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A positive effect of estrogen treatment has been observed in neurodegenerative diseases such as Parkinson's disease. Since 17β-estradiol can modulate positively dopaminergic system, here we sought to evaluate the effect of 17β-estradiol supplementation on an animal model developing dopaminergic alterations on nucleus of striatum after neonatal exposure to permethrin pesticide. The goal of the study was to verify if the co-treatment with 17β-estradiol could protect against the damage induced by pesticide exposure in early life. Permethrin treated rats showed a decrease of dopamine and Nurr1 gene expression in striatum, while a more pronounced decrease of dopamine was observed in rats co-administered with permethrin+17β-estradiol. No difference between control and permethrin treated rats was observed in both mRNA of ERα and ERβ, whereas the rats co-administered with permethrin+17β-estradiol showed a down-regulation of ERα expression. The in vitro studies showed that permethrin, at high concentration may have an antagonist effect on ERα and even more pronounced in ERβ, thus suggesting that permethrin may block the estrogen neuroprotective effects. In conclusion, in male rats, the administration of estrogen further enhanced the impairment of dopaminergic transmission due to exposure to permethrin.
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http://dx.doi.org/10.1016/j.chemosphere.2014.05.035 | DOI Listing |
Front Biosci (Landmark Ed)
August 2025
Department of Biomedical Sciences, University of Missouri-Kansas City, School of Medicine, Kansas City, MO 64108, USA.
Glutamate is an important neurotransmitter in the mammalian brain. Among the receptors that glutamate interacts with is metabotropic glutamate (mGlu) receptor 2, a Gα-coupled receptor. These receptors are primarily located on glutamatergic nerve terminals and act as presynaptic autoreceptors to produce feedback inhibition of glutamate release.
View Article and Find Full Text PDFJ Neurosci
September 2025
Faculty of Psychology, Southwest University, Chongqing, China
While the hyper- and hypo- reward or punishment sensitivities (RS, PS) have received considerable attention as prominent transdiagnostic features of psychopathology, the lack of an overarching neurobiological characterization currently limits their early identification and neuromodulation. Here we combined microarray data from the Allen Human Brain Atlas with a multimodal fMRI approach to uncover the neurobiological signatures of RS and PS in a discovery-replication design (N=655 healthy participants, 442 Females). Both RS and PS were mapped separately in the brain, with the functional connectome in the fronto-striatal network encoding reward responsiveness, while the fronto-insular system was particularly engaged in punishment sensitivity.
View Article and Find Full Text PDFFront Neurol
August 2025
Department of Rehabilitation, Shengjing Hospital of China Medical University, Shenyang, China.
The pathogenesis of Parkinson's disease (PD) is gradually evolving from a central neurodegeneration-centered concept to a multi-pathway pathological model at the gut-brain system level. Studies have shown that PD patients commonly exhibit dysbiosis, reduced short-chain fatty acids (SCFAs; microbial fermentation products of dietary fiber that play key roles in host metabolism and immune regulation), abnormal tryptophan metabolism, and impaired gut barrier function. These alterations may contribute to dopaminergic neuronal damage through mechanisms including neuroinflammation, oxidative stress, and α-synuclein (α-syn) aggregation.
View Article and Find Full Text PDFbioRxiv
August 2025
National Institute of Neurological Disorders and Stroke, 35 Convent Dr., Bldg. 35, Rm. 2B-1012, Bethesda, MD 20892.
The ATPase N-ethylmaleimide-sensitive factor (NSF), known for disassembling SNARE complexes, plays key roles in neurotransmitter release, neurotransmitter (AMPA, GABA, dopamine) receptor trafficking, and synaptic plasticity, and its dysfunction or mutation is linked to neurological disorders. These roles are largely attributed to SNARE-mediated exocytosis. Here, we reveal a previously unrecognized role for NSF: mediating diverse modes of endocytosis-including slow, fast, ultrafast, overshoot, and bulk-by driving closure of both fusion and fission pores.
View Article and Find Full Text PDFExpert Opin Ther Targets
September 2025
Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, NJ, USA.
Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a common neuropsychiatric disorder of inattention, hyperactivity, and impulsivity. Roles for dopamine and norepinephrine are widely recognized; however, the role of serotonergic neurotransmission is less clear. This systematic literature review aimed to determine if changes in serotonin transmission are implicated in the neurobiology of ADHD.
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