Adult hippocampal neurogenesis and its impairment in Alzheimer's disease

Adult neurogenesis is the creation of new neurons which integrate into the existing neural circuit of the adult brain.Recent evidence suggests that adult hippocampal neurogenesis(AHN)persists throughout life in mammals,including humans.These newborn neurons have been implicated to have a crucial role in brain functions such as learning and memory.Importantly,studies have also found that hippocampal neurogenesis is impaired in neurodegenerative and neuropsychiatric diseases.Alzheimer’s disease(AD)is one of the most common forms of dementia affecting millions of people.Cognitive dysfunction is a common symptom of AD patients and progressive memory loss has been attributed to the degeneration of the hippocampus.Therefore,there has been growing interest in identifying how hippocampal neurogenesis is affected in AD.However,the link between cognitive decline and changes in hippocampal neurogenesis in AD is poorly understood.In this review,we summarized the recent literature on AHN and its impairments in AD.

The radial organization of neuronal primary cilia is acutely disrupted by seizure and ischemic brain injury

BACKGROUND： Neuronal primary cilia are sensory organelles that are critically involved in the proper growth, development, and function of the central nervous system （CNS）. Recent work also suggests that they signal in the context of CNS injury, and that abnormal ciliary signaling may be implicated in neurological diseases. METHODS： We quantified the distribution of neuronal primary cilia alignment throughout the normal adult mouse brain by immunohistochemical staining for the primary cilia marker adenylyl cyclase Ⅲ （ACⅢ） and measuring the angles of primary cilia with respect to global and local coordinate planes. We then introduced two different models of acute brain insult--temporal lobe seizure and cerebral ischemia, and re-examined neuronal primary cilia distribution, as well as ciliary lengths and the proportion of neurons harboring cilia. RESULTS： Under basal conditions, cortical cilia align themselves radially with respect to the cortical surface, while cilia in the dentate gyms align themselves radially with respect to the granule cell layer. Cilia of neurons in the striatum and thalamus, by contrast, exhibit a wide distribution of ciliary arrangements. In both cases of acute brain insult, primary cilia alignment was significantly disrupted in a region-specific manner, with areas affected by the insult preferentially disrupted. Further, the two models promoted differential effects on ciliary lengths, while only the ischemia model decreased the proportion of ciliated cells. CONCLUSIONS： These findings provide evidence for the regional anatomical organization of neuronal primary cilia in the adult brain and suggest that various brain insults may disrupt this organization.

Centrosome positioning and primary cilia assembly orchestrate neuronal development

Establishment of axon and dendrite polarity, migration to a desired location in the developing brain, and establishment of proper synaptic connections are essential processes during neuronal development. The cellular and molecular mechanisms that govern these processes are under intensive investigation. The function of the centrosome in neuronal development has been examined and discussed in few recent studies that underscore the fundamental role of the centrosome in brain development. Clusters of emerging studies have shown that centrosome positioning tightly regulates neuronal development, leading to the segregation of cell factors, directed neurite differentiation, neuronal migration, and synaptic integration. Furthermore, cilia, that arise from the axoneme, a modified centriole, are emerging as new regulatory modules in neuronal development in conjunction with the centrosome. In this review, we focus on summarizing and discussing recent studies on centrosome positioning during neuronal development and also highlight recent findings on the role of cilia in brain development. We further discuss shared molecular signaling pathways that might regulate both centrosome and cilia associated signaling in neuronal development. Furthermore, molecular determinants such as DISC1 and LKB1 have been recently demonstrated to be crucial regulators of various aspects of neuronal development. Strikingly, these determinants might exert their function, at least in part, via the regulation of centrosome and cilia associated signaling and serve as a link between these two signaling centers. We thus include an overview of these molecular determinants.

Hypothalamic-Modified New Hippocampal Neurons for Alzheimer’s Disease

Alzheimer's disease(AD)is the leading cause of dementia worldwide.Although its pathology has been extensively studied,treatment options for AD remain limited.Any option to enhance the plasticity in the degenerating brain renders a potential treatment pathway for AD.