Neuroscience
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Brain microvascular endothelial cell (BMEC) injury induced by ischemia-reperfusion (I/R) is the initial stage of blood-brain barrier (BBB) disruption, which results in a poor prognosis in ischemic stroke patients. Autophagy has been shown to have protective effects on BMECs against cerebral ischemic insults. However, molecular mechanism of BMEC autophagy during I/R is unclear. ⋯ We further explored the molecular mechanisms by which Malat1 exerted regulatory effects, and found that Malat1 served as an endogenous sponge to downregulate miR-26b expression by binding directly to miR-26b. Furthermore, Malat1 overturned the inhibitory effect of miR-26b on BMEC autophagy and survival, which involved in promoting the expression of miR-26b target ULK2. Collectively, our study illuminated a new Malat1-miR-26b-ULK2 regulatory axis in which Malat1 served as a competing endogenous RNA by sponging miR-26b and upregulating ULK2 expression, thereby promoting BMEC autophagy and survival under OGD/R condition.
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Tauopathies are a class of neurodegenerative diseases associated with the pathological aggregation of tau protein in the human brain. Although numerous studies in mouse models of Alzheimer disease (AD) have shown a correlation among diet, beta-amyloid and AD onset, little is known about the impact of diet on Tau. We investigated whether a low fat-protein diet (LFPD) may improve lifespan, cognitive and locomotor activity in P301L-tg mouse model of tauopathy. ⋯ For instance, tg females, but not males, fed with LFPD had a significant increase of body weight and a reduction of P-Tau agglomerates compared to tg fed with standard diet. These changes correlated with a more pronounced improvement of cognition and locomotor activity in females than in male tg fed with LFPD. Altogether, these results suggest a sex dependent neuroprotective effect of LFPD in P301L-tg mice, suggesting that lifestyle intervention strategies may be clinically relevant for delaying the onset of cognitive impairment and dementia, especially in females.
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Brain glucose metabolism is altered in sporadic Alzheimer's disease (sAD), whose pathologies are reproduced in rodents by intracerebroventricular (icv) infusion of streptozotocin (STZ) in subdiabetogenic doses. The icv-STZ model also culminates in central cholinergic dysfunctions, which in turn are known to underlie both the sAD cognitive decline, and synaptic plasticity impairments. Considering the cognitive-enhancing potential of chronic nicotine (Nic), we investigated whether it attenuates icv-STZ-induced impairments in recognition memory and synaptic plasticity in a cognition-relevant substrate: the hippocampal CA1-medial prefrontal cortex (mPFC) pathway. ⋯ We found that Nic treatment prevents icv-STZ-induced disruptions in recognition memory and LTP. STZ did not precipitate neuronal death, while Nic alone was associated with higher neuronal density in CA1 when compared to vehicle-injected animals. Through combining behavioral, neurophysiological, and neuropathological observations into the Nic-STZ interplay, our study reinforces that cholinergic treatments are of clinical importance against early-stage Alzheimer's disease and mild cognitive impairments.
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Numerous clinical and experimental observations suggest that deficient neuronal signaling in the globus pallidus externa (GPe) is integral to both Parkinson's disease (PD) and dystonia. In our previous studies in jaundiced dystonic rats, widespread silencing of neurons in GP (rodent equivalent to GPe) preceded and persisted during dystonic motor activity. We therefore hypothesized that on a background of slow and highly irregular and bursty neuronal activity in GP, cortical motor drive produces profound inhibition of GP as the basis for action-induced dystonia in Gunn rats. ⋯ Next, we compared the deep brain stimulation contact sites in the GP internus used to treat patients with PD (n=21 implants in 12 successive patients) versus dystonia (n=16 implants in nine patients) and found the efficacious territory for ameliorating PD to be located chiefly dorsal to that for dystonia. The comparative distribution for treating PD versus dystonia was therefore anatomically consistent with that for inducing these features via GP lesions in rodents. Our collective findings thus suggest that dystonia and parkinsonism are differentially produced by pathological silencing of GPe neurons along distinct motor sub-circuits, resulting in disparate pathological basal ganglia output signaling.
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Neuroscientific research has made a concerted effort to determine cortical localization using various functional imaging techniques. This approach has undoubtedly yielded important novel anatomical knowledge, albeit at times contradictory, regarding the structural organization of the vestibular cortex. Unfortunately however, this knowledge has not translated to our understanding regarding how neural mechanisms control vestibular function. ⋯ Contrastingly, in the second half of this review, I present previous findings that show how disrupting interhemispheric interactions can modulate the brainstem-mediated vestibular-ocular reflex (VOR). I conclude by speculating why interhemispheric competition induces correlated biases at the cortical and brainstem level respectively. Specifically, I propose that brainstem-mediated vestibulo-spatial and vestibulo-temporal transformations, in addition to coding for head displacement, underpin a generalized cortical magnitude estimation system which the CNS uses to construct dynamic spatio-temporal maps of the physical world, in-turn ensuring spatial orientation.