Neuroscience
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Sexually dimorphic neural structures regulate numerous gender-specific functions including luteinizing hormone (LH) release patterns. The female cyclic surge pattern of release is controlled by the anteroventral periventricular nucleus (AVPV), a preoptic area (POA) region that is significantly smaller in males. The prevailing hypothesis used to explain these differences in structure and function is that a "default" feminine AVPV is defeminized by exposure to estradiol (E2), a metabolite of testosterone (T) produced by the perinatal testes. ⋯ Quantitative polymerase chain reaction (QPCR) studies confirmed higher mRNA levels in PND2 male and E2-treated female AVPVs wherein E2 induces apoptosis. POA mapping studies detected Cugbp2 mRNA in the AVPV and in the sexually dimorphic nucleus of the POA (SDN-POA); however, sex differences and E2 effects occurred only in the AVPV. Combined with evidence that Cugbp2 regulates splicing and translation of mRNAs linked to sexual differentiation, we propose that this gene mediates E2-dependent effects on AVPV defeminization.
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Taste aversion learning is a type of conditioning where animals learn to associate a novel taste (conditioned stimulus; CS) with a stimulus inducing symptoms of poisoning or illness (unconditioned stimulus; US). As a consequence animals later avoid this taste, a reaction known as conditioned taste aversion (CTA). An established CTA extinguishes over time when the CS is repeatedly presented in the absence of the US. ⋯ Moreover, the latter animals showed increased c-fos mRNA expression in the insular cortex. Our data indicate that CTA extinction apparently depends on the strength of the initially learned CS-US association. In addition, these findings provide further evidence that the memory for the initial excitatory conditioning and its subsequent extinction is probably stored in those structures that participate in the processing of the CS and the US.
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Fragile X syndrome (FXS) is an inherited neurodevelopmental disorder affecting nearly one in 5000 newborn males and is a leading genetic cause of autism spectrum disorder. In addition to developmental delays and intellectual impairment, FXS is characterized by seizures, attention deficit, and hypersensitivity to visual, tactile and auditory stimuli. The Fmr1 gene encodes Fragile X mental retardation protein (FMRP), which is abundant in neurons, binds select mRNAs and functions as a negative regulator of mRNA translation. ⋯ Additionally, neurons in the medial superior olive (MSO) were more round in Fmr1 KO rats. There was also reduced expression of glutamic acid decarboxylase (GAD67) in neurons of the superior paraolivary nucleus (SPON) and a reduction in the number of calretinin-immunoreactive terminals associated with neurons of the medial nucleus of the trapezoid body (MNTB). Together, these findings support the conclusion that the auditory dysfunction characteristic of FXS arises, at least in part, from defective brainstem networks.
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Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder with increased oxidative stress, the underlying vital process contributing to cell death. Tanshinone IIA (Tan IIA), a major bioactive diterpene quinone of Salva miltiorrhiza, had been proved effective in the MPTP model through its anti-inflammatory activity. Here in this research, we found that Tan IIA prevented the loss of nigrostriatal dopaminergic neurons by activating the NF-E2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway. ⋯ Further studies revealed that Tan IIA reduced the enhancement of miR-153 by 6-OHDA, which targeted the 3'-UTR of Nrf2, and suppressed its expression and activation. Additionally, neurodegeneration caused by in vivo stereotaxic injection of 6-OHDA could also be ameliorated by the administration of Tan IIA. Taken together, our results strongly suggest that Tan IIA may be beneficial for the treatment of PD, and also confirm that targeting the Nrf2/ARE pathway is a promising strategy for therapeutic intervention in PD.
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Increased understanding of the neurovascular niche suggests that development of the central nervous system (CNS) and its vasculature is coordinated through shared regulatory factors. These include the vascular endothelial growth factor (VEGF) family, reported to promote neuroproliferation and neuroprotection in addition to angiogenesis via its receptors VEGFR1-3. VEGFR3, a mediator of lymphangiogenesis, is expressed in murine and rat brain from early gestation, has been associated with neural progenitors and neurons (Choi et al., 2010) and oligodendroglia (Le Bras et al., 2006) in the developing cortex and is reported to mediate adult neurogenesis in the subventricular zone (SVZ) (Calvo et al., 2011). ⋯ High expression in ventricular ependyma, choroid plexus and pigmented retinal epithelium was noted from E18. VEGFC ligand was found in association with VEGFR3 throughout development, with highest expression in embryonic stages. Our findings suggest an important role for VEGFC/VEGFR3 signaling in neuronal proliferation in early forebrain development, and ongoing functions with niche neurogenesis, glial and ependymal function in the maturing postnatal brain.