Several genes, such as Septin-14, are particularly prevalent in the embryonic and newborn brain, signaling an essential function in guiding, structuring, and pruning the early-life brain's developing neuronal circuits and modules. Chen et al. revealed that in both sexes of adult mice, deletion of the Septin-14 gene enhances ventral hippocampus DG cell proliferation and stress-induced anxiety while decreasing observational fear conditioning magnitudes. While multiple septin GTPases have been found for physiological purposes, less emphasis has been paid to their roles in coordinating advanced cognitive/emotional functions in mature animals. The sexually dimorphic effects of brain SEPT14 KO on inhibitory avoidance (IA) and hippocampal mGluR5 expression were only seen in male KO mice, who had longer IA latency and higher mGluR5 levels. Furthermore, independent of the animals' sexes, SEPT14 KO was linked with increased stress-induced anxiety in a stress-related navigation task. While male and female WT mice showed similar cell proliferation in the dorsal and ventral hippocampal dentate gyrus (DG), SEPT14 KO mice had increased cell proliferation in the ventral DG in both sexes (Chen et al.). Overall, these findings suggest that male, but not female, mice lacking the Septin-14 gene have higher unpleasant emotion-related learning and dorsal/ventral hippocampus mGluR5 expression, which can be linked to increased ventral hippocampus DG cell proliferation and stress-induced anxiety-like behavior, while decreasing vicarious fear conditioning magnitudes.

Growing evidence shows that aberrant α-syn accumulation in the hippocampus might lead to cognitive impairment. Overexpression of α-syn in nuclei was shown by Pan et al. to induce considerable pathological accumulation of α-syn in the hippocampus, leading to memory and motor deficits in mice. Nuclear overexpression of α-syn is thought to cause DNA damage in hippocampus neurons, resulting in activation, aberrant cell cycle blockage, hippocampal neuron death, and inflammatory response. Meanwhile, the inflammatory response exacerbated DNA damage and created a vicious cycle, resulting in Parkinson's disease symptoms (Pan et al.).

Obesity has become a pandemic in recent decades and is often regarded as one of the world's most serious public health issues. Obesity caused by a high-fat diet (HFD) significantly contributes to decreased memory and cognitive function, but the underlying processes remain unknown. The current study examined the amounts of circRNAs in the hippocampus of C57BL/6J mice and the memory and cognitive abilities of C57BL/6J mice fed HFD utilizing the Morris water maze and Y-maze methods. HFD-induced obesity mice with variable circRNA expression (mmu-circRNA-004797 and mmu-circRNA-21040) demonstrated decreased synaptic plasticity and endoplasmic reticulum stress in hippocampus neurons with obesity-associated cognitive impairment (Niu et al.). This study revealed that circRNAs play crucial functions and are most likely implicated in obesity-related cognitive impairment susceptibility.

Interestingly, Huang et al. evaluated the relationship between hand grip strength and cognitive decline in elderly Americans. On 2,623 people aged 60 years, the Consortium to Establish a Registry for Alzheimer's Disease (CERAD < 5), animal fluency (AF < 14), and digit symbol substitution test (DSST < 34) scores were used to assess cognitive impairment (Huang et al.). They discovered an inverse link between hand grip strength and cognitive impairment, which might point to a common underlying mechanism that should be studied further in large-scale prospective clinical studies.

TBI is one of the top causes of death and disability worldwide, with a complex and variable process. Glutamate-induced excitotoxicity, oxidative stress, inflammatory response, ion imbalance, and metabolic disarray, for example, are all important pathogenic alterations that lead to neuronal death (Rosenfeld et al., 2012). While high calcium influx causes mitochondrial disintegration, increased BBB permeability and lactic acidosis create cerebral edema, intracranial hypertension causes distinct pathologic alterations (Maas et al., 2017). Here, neurological abnormalities exist from the acute to the subacute stages, and brain parenchyma was significantly affected at either stage. The dynamic pathophysiology of these stages revealed candidate targets ranging from platelet activation to nerve-related pathways to some aberrant secretions that were crucial in the acute phase. The considerable enrichment of amyotrophic lateral sclerosis, on the other hand, alerts us to the continuation of nerve damage into the subacute phase, implying that neuroprotective intervention should be implemented at the earliest stage of severe traumatic brain injury to minimize cognitive motor dysfunction (Luo et al.).