Browsing by Subject "Neurodegeneration"

Now showing 1 - 17 of 17
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    A New Tool to Study Parkinsonism in the Context of Aging: MPTP Intoxication in a Natural Model of Multimorbidity
    (MDPI, ) Cuenca, Lorena; Pizzichini, Elisa; Gonçalves, Valeria C.; Guillén Díaz, María; Aguilar Moñino, Elena; Sánchez Rodrigo, Consuelo; González Cuello, Ana María; Fernández Villalba, Emiliano; Herrero Ezquerro, María Trinidad; Enfermería
    The diurnal rodent Octodon degus (O. degus) is considered an attractive natural model for Alzheimer’s disease and other human age-related features. However, it has not been explored so far if the O. degus could be used as a model to study Parkinson’s disease. To test this idea, 10 adult male O. degus were divided into control group and MPTP-intoxicated animals. Motor condition and cognition were examined. Dopaminergic degeneration was studied in the ventral mesencephalon and in the striatum. Neuroinflammation was also evaluated in the ventral mesencephalon, in the striatum and in the dorsal hippocampus. MPTP animals showed significant alterations in motor activity and in visuospatial memory. Postmortem analysis revealed a significant decrease in the number of dopaminergic neurons in the ventral mesencephalon of MPTP animals, although no differences were found in their striatal terminals. We observed a significant increase in neuroinflammatory responses in the mesencephalon, in the striatum and in the hippocampus of MPTP-intoxicated animals. Additionally, changes in the subcellular expression of the calcium-binding protein S100 were found in the astrocytes in the nigrostriatal pathway. These findings prove for the first time that O. degus are sensitive to MPTP intoxication and, therefore, is a suitable model for experimental Parkinsonism in the context of aging.
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    An insight into the role of autophagy in cell responses in the aging and neurodegenerative brain
    (F. Hernandez y JuanF. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología., 2012) Caballero, B; Coto-Montes, A.
    Oxidative stress, inflammation and the aggregation of oxidized, misfolded or aberrant proteins in the brain induces deregulations in programmed cell death: apoptosis and autophagy. Apoptosis is one of processes implicated in aging and neurodegenerative pathologies, and for the last decade, has been one of the most studied processes due to its essential role, not only in aging, but also in many neurodegenerative diseases, including Parkinson’s, Alzheimer’s and Huntington’s. However, autophagy being the major intracellular pathway for the degradation and recycling of long-live proteins and organelles is widely involved in the pathogenesis or prevention of many age-related diseases, including neurodegenerative conditions. Recently, autophagy activation has been considered as part of the cellular responses to elevated oxidative stress, eliminating unwanted, damaged and oxidative structures; thus favouring, in this way, the key anti-aging mechanism associated with the caloric restriction. Longevity factors, such as sirtuins, and redox-sensitive transcriptional factors, such as NF-κB and p53, can also regulate basal autophagy in cells, with a direct impact on longevity and the development of inflammation and neurodegeneration. Here, we reviewed the critical changes of autophagy in the aging and neuro-degenerative brain and the role of key regulators of autophagy, which are directly related to oxidative stress, inflammation and longevity pathways.
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    Bidirectional gut-to-brain and brain-to-gut propagation of synucleinopathy in non-human primates
    (Oxford University Press, 2020-05-07) Arotcarena, Marie-Laure; Dovero, Sandra; Prigent, Alice; Bourdenx, Mathieu; Camus, Sandrine; Porras, Gregory; Thiolat, Marie-Laure; Tasselli, Maddalena; Aubert, Philippe; Kruse, Niels; Mollenhauer, Brit; Trigo Damas, Ines; Estrada, Cristina; Garcia-Carrillo, Nuria; Vaikath, Nishant; El-Agnaf, Omar M.A.; Vila, Miquel; Obeso, Jose A.; Derkinderen, Pascal; Dehay, Benjamin; Bezard, Erwan; Herrero Ezquerro, María Trinidad; Anatomía Humana y Psicobiología
    In Parkinson’s disease, synucleinopathy is hypothesized to spread from the enteric nervous system, via the vagus nerve, to the CNS. Here, we compare, in baboon monkeys, the pathological consequences of either intrastriatal or enteric injection of a-synucleincontaining Lewy body extracts from patients with Parkinson’s disease. This study shows that patient-derived a-synuclein aggregates are able to induce nigrostriatal lesions and enteric nervous system pathology after either enteric or striatal injection in a non-human primate model. This finding suggests that the progression of a-synuclein pathology might be either caudo-rostral or rostro-caudal, varying between patients and disease subtypes. In addition, we report that a-synuclein pathological lesions were not found in the vagal nerve in our experimental setting. This study does not support the hypothesis of a transmission of a-synuclein pathology through the vagus nerve and the dorsal motor nucleus of the vagus. Instead, our results suggest a possible systemic mechanism in which the general circulation would act as a route for long-distance bidirectional transmission of endogenous a-synuclein between the enteric and the central nervous systems. Taken together, our study provides invaluable primate data exploring the role of the gut-brain axis in the initiation and propagation of Parkinson’s disease pathology and should open the door to the development and testing of new therapeutic approaches aimed at interfering with the development of sporadic Parkinson’s disease.
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    Brain injections of glial cytoplasmicinclusions induce a multiple systematrophy-like pathology
    (Oxford University Pres, 2022-03-14) Margaux, Teil; Dovero, Sandra; Bourdenx, Mathieu; Arotcarena, Marie-Laure; Camus, Sandrine; Porras, Gregory; Thiolat, Marie-Laure; Trigo-Damas, Ines; Perier, Celine; Estrada, Cristina; Garcia-Carrillo, Nuria; Morari, Michele; Meissner, Wassilios G.; Vila, Miquel; Obeso, Jose A.; Bezard, Erwan; Dehay, Benjamin; Herrero Ezquerro, María Trinidad; Anatomía Humana y Psicobiología
    Synucleinopathies encompass several neurodegenerative diseases, which include Parkinson’s disease, dementiawith Lewy bodies and multiple system atrophy. These diseases are characterized by the deposit ofa-synucleinaggregates in intracellular inclusions in neurons and glial cells. Unlike Parkinson’s disease and dementia withLewy bodies, where aggregates are predominantly neuronal, multiple system atrophy is associated witha-synu-clein cytoplasmic inclusions in oligodendrocytes. Glial cytoplasmic inclusions are the pathological hallmark ofmultiple system atrophy and are associated with neuroinflammation, modest demyelination and, ultimately, neu-rodegeneration.To evaluate the possible pathogenic role of glial cytoplasmic inclusions, we inoculated glial cytoplasmic inclusion-containing brain fractions obtained from multiple system atrophy patients into the striatum of non-human pri-mates. After a 2-yearin vivophase, extensive histochemical and biochemical analyses were performed on thewhole brain.We found loss of both nigral dopamine neurons and striatal medium spiny neurons, as well as loss of oligodendro-cytes in the same regions, which are characteristics of multiple system atrophy. Furthermore, demyelination, neu-roinflammation anda-synuclein pathology were also observed. These results show that thea-synuclein species inmultiple system atrophy-derived glial cytoplasmic inclusions can induce a pathological process in non-human pri-mates, including nigrostriatal and striatofugal neurodegeneration, oligodendroglial cell loss, synucleinopathy andgliosis.The present data pave the way for using this experimental model for MSA research and therapeutic development
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    Cardiac Changes in Parkinson’s Disease: Lessons from Clinical and Experimental Evidence
    (MDPI, 2021-12) Herrero Ezquerro, María Trinidad; Laorden Carrasco, María Luisa; Cuenca Bermejo, Lorena; Almela Rojo, Pilar; Navarro Zaragoza, Javier; González Cuello, Ana María; Fernández Villalba, Emiliano; Enfermería
    Dysautonomia is a common non-motor symptom in Parkinson’s disease (PD). Most dysautonomic symptoms appear due to alterations in the peripheral nerves of the autonomic nervous system, including both the sympathetic and parasympathetic nervous systems. The degeneration of sympathetic nerve fibers and neurons leads to cardiovascular dysfunction, which is highly prevalent in PD patients. Cardiac alterations such as orthostatic hypotension, heart rate variability, modifications in cardiogram parameters and baroreflex dysfunction can appear in both the early and late stages of PD, worsening as the disease progresses. In PD patients it is generally found that parasympathetic activity is decreased, while sympathetic activity is increased. This situation gives rise to an imbalance of both tonicities which might, in turn, promote a higher risk of cardiac damage through tachycardia and vasoconstriction. Cardiovascular abnormalities can also appear as a side effect of PD treatment: L-DOPA can decrease blood pressure and aggravate orthostatic hypotension as a result of a negative inotropic effect on the heart. This unwanted side effect limits the therapeutic use of L-DOPA in geriatric patients with PD and can contribute to the number of hospital admissions. Therefore, it is essential to define the cardiac features related to PD for the monitorization of the heart condition in parkinsonian individuals. This information can allow the application of intervention strategies to improve the course of the disease and the proposition of new alternatives for its treatment to eliminate or reverse the motor and non-motor symptoms, especially in geriatric patients.
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    Combined 1-Deoxynojirimycin and Ibuprofen treatment decreases microglial activation, phagocytosis and dopaminergic degeneration in MPTP-treated mice
    (Springer , 2020-06-21) Costa, T. C. S.; Fernández Villalba, Emiliano; Izura, V.; Lucas Ochoa, a. M.; Menezes Filho, N. J.; Santana, R.; Olivera, M. de; Araújo, F.; Estrada Esteban, C.; Silva, V.; Costa, S. L.; Herrero Ezquerro, María Trinidad; Medicina Interna; Facultades de la UMU::Facultad de Medicina
    Inflammation is a predominant aspect of neurodegenerative diseases and experimental studies performed in animal models of Parkinson's disease (PD) suggesting that a sustained neuroinflammation exacerbates the nigrostriatal degeneration pathway. The central role of microglia in neuroinflammation has been studied as a target for potential neuroprotective drugs for PD, for example nonsteroidal anti-inflammatory drugs (NSAIDs) and matrix metalloproteinases (MMP) inhibitors that regulates microglial activation and migration. The aim of this study was to investigate the neuroprotective response of the iminosugar 1-deoxynojirimycin (1-DNJ) and compare its effect with a combined treatment with ibuprofen. MPTP-treated mice were orally dosed with ibuprofen and/or 1-DNJ 1. Open-field test was used to evaluate behavioral changes. Immunohistochemistry for dopaminergic neurons marker (TH+) and microglia markers (Iba-1+; CD68+) were used to investigate neuronal integrity and microglial activation in the substantia nigra pars compacta (SNpc). The pro-inflammatory cytokines TNF-α and IL-6 were analysed by qPCR. Treatments with either 1-DNJ or Ibuprofen alone did not reduce the damage induced by MPTP intoxication. However, combined treatment with 1-DNJ and ibuprofen prevents loss of mesencephalic dopaminergic neurons, decreases the number of CD68+/ Iba-1+ cells, the microglia/neurons interactions, and the pro-inflammatory cytokines, and improves behavioral changes when compared with MPTP-treated animals. In conclusion, these data demonstrate that the combined treatment with a MMPs inhibitor (1-DNJ) plus an anti-inflammatory drug (ibuprofen) has neuroprotective effects open for future therapeutic interventions. Graphical Abstract MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a protoxicant that, after crossing the Blood Brain Barrier, is metabolized by astrocytic MAO-B to MPDP+, a pyridinium intermediate, which undergoes further two-electron oxidation to yield the toxic metabolite MPP+ (methyl-phenyltetrahydropyridinium) that is then selectively transported into nigral neurons via the mesencephalic dopamine transporter. In this study, we demonstrated that MPTP induced death of dopaminergic neurons, microgliosis, increase of gliapses, motor impairment and neuroinflammation in mice, which were inhibited by combined 1-deoxynojirimycin and ibuprofen treatment.
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    Connecting cytokines and brain A review of current issues
    (Murcia : F. Hernández, 2002) Quan, N.; Herkenham, M.
    Cytokines have been a multi-disciplinary research focus for over 2 decades. To date, there have been more than 15000 articles published concerning the relationship between cytokines and the central nervous system (CNS). Over half of these articles have been published in the last 5 years. From such vast number of studies, two major topics emerge as the critical issues: 1) how do cytokines modulate the functions of the CNS? 2) what is the role of cytokines in the pathogenesis of neurological diseases? Thus far, it has been clearly established that cytokines can alter the functions of the CNS in specific manners, invoking CNS-controlled autonomic, neuroendocrine, and behavioral responses. Induced expression of cytokines has also been found in the CNS during brain injury and infection, contributing to the immunological processes at this “immunologically privileged” site. Furthermore, increasing evidence points to the potential involvement of cytokines in the induction and modulation of an array of neurological diseases ranging from Alzheimer’s disease to chronic fatigue syndrome. Despite such progress, however, substantial obstacles remain for both the basic understanding and the potential clinical exploitation of how cytokines interact with CNS. In this review, we will attempt to synopsize the current theories and evidence regarding the answers to the above-mentioned critical questions. These issues will be reviewed not only in isolation, as most of the original reports focused on only one of the questions, but also in parallel such that interissue insights may be gained.
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    Especies reactivas de oxígeno y su implicación en Biomedicina
    (Universidad de Murcia. Servicio de publicaciones, 2018) Lozano Picazo, Carmen María; Fernández-Belda, Francisco
    Las especies reactivas de oxígeno (ROS) actúan como regulador intracelular cuando se generan de forma controlada en puntos concretos de la célula. Modifican la función de proteínas mediante la oxidación reversible de cisteínas. Hay quinasas y fosfatasas de proteínas, factores de transcripción y canales iónicos que están regu-lados por ROS. Estrés oxidativo y daño celular aparecen cuando los mecanismos antioxidantes de protección son incapaces de mantener bajo el nivel intracelular de ROS. En estas condiciones, ROS inducen pérdida de viabilidad celular en patologías degenerativas de corazón y cerebro y promueven proliferación celular ilimitada en procesos tumorales. La alteración de la función mitocondrial juega un papel clave en la generación del estrés oxidativo y por tanto es una diana terapéutica preferente para evitar o aminorar los daños oxidativos producidos por ROS.
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    Heart matters: cardiac dysfunction and other autonomic changes in Parkinson’s disease
    (SAGE Publications, 2021-02-15) Gonçalves, Valeria C. ; Cuenca Bermejo, Lorena; Fernández Villalba, Emiliano; Martin Balbuena, Sebastian; Fernandes, Maria Jose da Silva; Scorza, Carla A.; Herrero Ezquerro, María Trinidad; Medicina; Facultades de la UMU
    It has been more than 200 years since James Parkinson made the first descriptions of the disease that bears his name. Since then, knowledge about Parkinson’s disease has been improved, and its pathophysiology, diagnosis, and treatments are well described in the scientific and medical literature. However, there is no way to prevent the disease from its progressive nature yet and only its symptoms can be minimized. It is known that the process of neurodegeneration begins before the onset of motor signs and symptoms of the disease, when diagnosis is usually made. Therefore, recognizing manifested non-motor symptoms can make an early diagnosis possible and lead to a better understanding of the disease. Autonomic dysfunctions are important non-motor manifestations of Parkinson’s disease and affect the majority of patients. Importantly, heart failure is the third leading cause of death in people suffering from Parkinson’s disease. Several evidences have shown the correlation between Parkinson’s disease and the preexistence of cardiovascular diseases. Therefore, cardiovascular monitoring and identification of its dysfunctions can have a prodromal role for Parkinson’s disease. This review presents studies of the literature that can lead to a better understanding of Parkinson’s disease with special attention to its relation to heart and cardiovascular parameters.
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    Identification of differentially expressed genes profiles in a combined mouse model of Parkinsonism and colitis
    (Nature research, ) Cuenca, L.; González Cuello, A.; Sánchez Rodrigo, C.; Parrado, A.; Vyas, S.; Herrero Ezquerro, María Trinidad; Gil Martínez, Ana Luisa; Fernández Villalba, Emiliano; Enfermería
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    Immunohistochemical characterization of Fas (CD95) and Fas Ligand (FasL-CD95L) expression in the injured brain: Relationship with neuronal cell death and inflammatory mediators
    (Murcia : F. Hernández, 2007) Grosjean, M.B.; Lenzlinger, P.M.; Stahel, P.F.; Yatsiv, I.; Shohami, E.; Trentz, O.; Kossmann, T.; Morganti-Kossmann, M.C.
    Traumatic brain injury causes progressive tissue atrophy and consequent neurological dysfunction, resulting from neuronal cell death in both animal models and patients. Fas (CD95) and Fas ligand (FasL/CD95L) are important mediators of apoptosis. However, little is known about the relationship between Fas and FasL and neuronal cell death in mice lacking the genes for inflammatory cytokines. In the present study, double tumor necrosis factor/lymphotoxin-a knockout (–/–) and interleukin-6–/– mice were subjected to closed head injury (CHI) and sacrificed at 24 hours or 7 days postinjury. Consecutive brain sections were evaluated for Fas and FasL expression, in situ DNA fragmentation (terminal deoxynucleotidyl transferase-mediated dUTPbiotin nick end-labeling; TUNEL), morphologic characteristics of apoptotic cell death and leukocyte infiltration. A peak incidence of TUNEL positive cells was found in the injured cortex at 24 hours which remained slightly elevated at 7 days and coincided with maximum Fas expression. FasL was only moderately increased at 24 hours and showed maximum expression at 7 days. A few TUNEL positive cells were also found in the ipsilateral hippocampus at 24 hours. Apoptotic, TUNEL positive cells mostly co-localized with neurons and Fas and FasL immunoreactivity. The amount of accumulated polymorphonuclear leukocytes and CD11b positive cells was maximal in the injured hemispheres at 24 hours. We show strong evidence that Fas and FasL might be involved in neuronal apoptosis after CHI. Furthermore, Fas and FasL upregulation seems to be independent of neuroinflammation since no differences were found between cytokine–/– and wild-type mice.
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    Metalloproteinase-9 contributes to inflammatory glia activation and nigro-striatal pathway degeneration in both mouse and monkey models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism.
    (2015) Anesse, V.; Gómez López, A.; De Pablos Vicente, V.; Fernández Villalba, Emiliano; Herrero Ezquerro, María Trinidad; Anatomía Humana y Psicobiología
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    Molecular mechanisms in the pathogenesis of traumatic brain injury
    (Murcia : F. Hernández, 2002) Ray, S.K.; Dixon, C.E.; Banik, N.L.
    Traumatic brain injury (TBI) is a serious neurodisorder commonly caused by car accidents, sports related events or violence. Preventive measures are highly recommended to reduce the risk and number of TBI cases. The primary injury to the brain initiates a secondary injury process that spreads via multiple molecular mechanisms in the pathogenesis of TBI. The events leading to both neurodegeneration and functional recovery after TBI are generalized into four categories: (i) primary injury that disrupts brain tissues; (ii) secondary injury that causes pathophysiology in the brain; (iii) inflammatory response that adds to neurodegeneration; and (iv) repair-regeneration that may contribute to neuronal repair and regeneration to some extent following TBI. Destructive multiple mediators of the secondary injury process ultimately dominate over a few intrinsic protective measures, leading to activation of cysteine proteases such as calpain and caspase-3 that cleave key cellular substrates and cause cell death. Experimental studies in rodent models of TBI suggest that treatment with calpain inhibitors (e.g., AK295, SJA6017) and neurotrophic factors (e.g., NGF, BDNF) can prevent neuronal death and dysfunction in TBI. Currently, there is still no precise therapeutic strategy for the prevention of pathogenesis and neurodegeneration following TBI in humans. The search continues to explore new therapeutic targets and development of promising drugs for the treatment of TBI.
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    Neural stem cells and the quest for restorative neurology
    (Murcia : F. Hernández, 2004) Luque, J.M.; Giménez y Ribotta, M.
    A great deal of interest has attracted the attention of researchers on the potential use of (neural) stem cells in cell replacement or restorative therapies for heretofore incurable CNS pathologies such as brain stroke, spinal cord injury, Parkinson’s disease or multiple sclerosis. This short perspective illustrates our view of neural stem cell research with a focus on the stem cell concept, on the in situ identity of neural stem cells and on selected aspects of embryonic and adult neurogenesis. A brief survey of current stem cell-based experimental literature tries to provide a realistic picture of how far we have gone in the quest to establish a restorative neurology.
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    Novel features of neurodegeneration in the inner retina of early diabetic rats
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Énzsöly, Anna; Szabó, Arnold; Szabó, Klaudia; Szél, Ágoston; Németh, János; Lukáts, Ákos
    The literature indicates that in diabetes retinal dysfunctions related to neural retinal alterations exist prior to clinically detectable vasculopathy. In a previous report, a detailed description about the alteration of the outer retina was given, where diabetic degeneration preceded apoptotic loss of cells (Enzsöly et al., 2014). Here, we investigated the histopathology of the inner retina in early diabetes using the same specimens. We examined rat retinas with immunohistochemistry and Western blotting, 12 weeks after streptozotocin induction of diabetes. Glial reactivity was observed in all diabetic retinal specimens; however, it was not detectable all over the retina, but appeared in randomly arranged patches, with little or no glia activation in between. Similarly, immunoreactivity of parvalbumin (staining mostly AII amacrine cells) was also decreased only in some regions. We propose that these focal changes appear prior to affecting the whole retina and overt loss of cells. In contrast to these, most other markers used (calretinin, recoverin, tyrosin hydroxylase anti-Brn-3a and also calbindin in the optic part of the retina) did not show any major alterations in the intensity of immunoreactivity or in the number of stained elements. Interestingly, under diabetic conditions, the labeling pattern of PKC-α and calbindin in the ciliary retina showed a clear resemblance to the pattern described during development. This observation is in line with our previous study, reporting an increase in the number of dual cones, coexpressing two photopigments, which is another common feature with developing retinas. These data may indicate a previously uninvestigated regenerative capacity in diabetic retina
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    Parkinson's disease: a short story of 200 years
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Cuenca, L.; Cano Fernandez, L.; Sanchez Rodrigo, C.; Estrada, C.; Fernández Villalba, Emiliano; Herrero Ezquerro, María Trinidad; Gil Martínez, Ana Luisa
    After Alzheimer’s disease, Parkinson’s disease (PD) is the second most prevalent and incidental neurodegenerative disorder, affecting more than 2% of the population older than 65 years old. Since it was first described 200 years ago by Dr James Parkinson, great steps have been made in the understanding of the pathology. However, the cause(s) that initiates and perpetuates the neurodegenerative process is (are) still not clear. Thus, early diagnosis is not available, nor are there efficient therapies that can stop neurodegeneration. PD clinical features are defined by motor (like bradykinesia, resting tremor, gait impairment) and nonmotor symptoms (like constipation, apathy, fathigue, olfactory dysfunction, depression and cognitive decline) that get more severe as the disease advances. Neuropathological hallmarks comprise selective loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc) and Lewy bodies (LB) in different nuclei of the nervous system. Numerous studies have shown that these pathological features are aggravated by the confluence of other contributing factors, such as a genetic component, exposure to environmental toxins, mitochondrial dysfunction, increase of oxidative stress, calcium imbalance and chronic neuroinflammation, among others. Here, we provide a summary of the actual state of PD’s pathology, the most studied molecular mechanisms, classic and novel therapeutic strategies and diagnosis methods, especially highlighting recent advances in these 200 years
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    Study of the link between neuronal death, glial response, and MAPK pathway in old parkinsonian mice
    (Frontiers Media, 2020-07-29) Cuenca-Bermejo L,; Gallo-Soljancic P,; Sanchez-Rodrigo C,; Izura V,; Steinbusch HWM,; Fernandez-Villalba E,; Herrero MT; Cuenca Bermejo, Lorena; Gallo-Soljancic, Pablo; Sanchez-Rodrigo, Consuelo; Izura, Virginia; Steinbusch, Harry W. M.; Fernández Villalba, Emiliano; Herrero Ezquerro, María Trinidad; Gil Martínez, Ana Luisa; Medicina Interna; Facultad de Medicina
    Parkinson's disease (PD) is described as an age-related neurodegenerative disorder. However, the vast majority of research is carried out using experimental models of young animals lacking the implications of the decline processes associated with aging. It has been suggested that several molecular pathways are involved in the perpetuation of the degeneration and the neuroinflammation in PD. Among others, mitogen-activated protein kinases (MAPKs) have been highly implicated in the development of PD, and regulating components of their activity are indicated as promising therapeutic targets. Methods: To further define how MAPKs expression is related to the glial response and neuronal cell death, Parkinsonism was induced under an acute regimen in old mice. Moreover, the sacrifice was carried out at different time points (4, 8, 24, and 48 h) after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) injections to describe the early dynamic changes over time produced by the intoxication. Results: The results revealed that neuronal death increases as glial response increases in the nigrostriatal pathway. It was observed that both processes increase from 4 h in the ventral mesencephalon (VM), and neuronal death becomes significant at 48 h. In the striatum, they were significantly increased from 48 h after the MPTP administration compared with that in the control mice. Moreover, the p-ERK levels decrease, while phospho-p38 expression increases specifically in the striatum at 48 h after MPTP intoxication. Conclusions: The importance of these data lies in the possibility of elucidating the underlying mechanisms of neurodegenerative processes under aging conditions to provide knowledge for the search of solutions that slow down the progression of PD.