Neuroscience
-
Individuals with Highly Superior Autobiographical Memory (HSAM) provide the opportunity to investigate the neurobiological substrates of enhanced memory performance. While previous studies started to assess the neural correlates of memory retrieval in HSAM, here we assessed for the first time the intrinsic connectivity of a core memory region, the hippocampus, with the whole brain, in 8 HSAM subjects (HSAMs) and 21 controls during resting-state functional neuroimaging. ⋯ This altered pattern of hippocampal rsFC might be interpreted as a reduced capability of HSAMs to discriminate and select salient information, with a subsequent increase in the probability to encode and consolidate sensory information irrespective of their task-relevancy. Ultimately, these findings provide evidence that HSAM might be paradoxically enabled by an altered hippocampal rsFC that bypasses regions involved with salience detection in favor of specialized sensory regions.
-
Morphine is an opioid drug often used in treating moderate to severe pain. However, morphine tolerance in patients limits its used in clinical settings. Our previous study showed that a cannabinoid type 2 (CB2) receptor agonist attenuated morphine tolerance. ⋯ The effect of the CB2 receptor agonist on morphine-induced downregulation of MKP-1 and MKP-3 was reversed by the MKP-1 and MKP-3 antagonist triptolide. Our findings suggested that CB2 receptor agonist may induce the expression of MKP-1 and MKP-3 to promote MAPK dephosphorylation and reduce the production of downstream cytokine, thereby reducing morphine tolerance. This finding suggested that MKPs may serve as a new target for alleviating morphine tolerance.
-
Ischemic injury in patients with stroke often leads to neuronal damage and mitochondrial dysfunction. Neuronal injury caused by ischemia can be partly attributed to glutamate (L-Glu) excitotoxicity. Previous studies have shown that PTEN-induced kinase 1 (PINK1) plays a neuroprotective role in ischemic brain injury by regulating mitochondrial integrity and function. ⋯ In addition, RAP (an autophagy activator) could increase the co-localization of the mitophagy-related proteins light chain 3 (LC3) and Tom20, whereas 3-MA (an autophagy inhibitor) exerted the opposite effect. Finally, we found that L-Glu could induce the expression of PINK1/Parkin/ LC3 in neurons at both mRNA and protein levels, while RAP could further increase their expression, and 3-MA decreased their expression. Taken together, PINK1 protects against L-Glu-induced neuronal injury by protecting mitochondrial function, and the potential protective mechanism may be closely related to the enhancement of mitophagy mediated by the PINK1/Parkin signaling pathway.
-
Decreased levels of Brain-Derived Neurotrophic Factor (BDNF) are a common finding in schizophrenia. Another well-documented protein linked to schizophrenia is intracellular Ca2+-independent Phospholipase (PLA2). However, the potential association between PLA2 and BDNF with regard to schizophrenia has yet to be examined. ⋯ The cognitive impairment of BDNF heterozygous mice as well as their increased PLA2 activity in plasma is consistent with findings in schizophrenia patients. The particular elevation of PLA2 activity in females may partly explain sex differences of clinical symptoms in schizophrenia (e.g. age of onset, severity of symptoms). Additionally, PLA2 was significantly correlated with body and adrenal weight after weaning, whereby the latter emphasizes the possible connection of PLA2 with steroidogenesis.
-
The prospect of exploiting memory reconsolidation to treat mental health disorders has received great research interest, particularly following demonstrations that the β-adrenergic receptor antagonist propranolol, which is safe for use in humans, can disrupt the reconsolidation of pavlovian conditioned fear memories. However, recent studies have failed to replicate the effects of propranolol on fear memory reconsolidation, and have questioned whether treatments based upon reconsolidation blockade would be robust enough for clinical translation. It remains possible, though, that studies reporting no effect of propranolol on memory reconsolidation could be due to a failure to engage the memory destabilisation process, which is necessary for the memory to become susceptible to disruption with amnestic agents. ⋯ Following a failure to replicate, we manipulated the parameters of the memory reactivation session to enhance prediction error in an attempt to overcome the boundary conditions of reconsolidation. On finding no disruption of memory despite these manipulations, we examined the expression of the post-synaptic density protein Shank in the basolateral amygdala. Degradation of Shank has been shown to correlate with the induction of memory lability, but we found no effect on Shank expression, consistent with the lack of observed behavioural effects.