Doublecortin-Expressing Neurons in Human Cerebral Cortex Layer II and Amygdala from Infancy to 100 Years Old

Abstract

A cohort of morphologically heterogenous doublecortin immunoreactive (DCX+) "immature neurons" has been identi ed in the cerebral cortex largely around layer II and the amygdala largely in the paralaminar nucleus (PLN) among various mammals. To gain a wide spatiotemporal view on these neurons in humans, we examined layer II and amygdalar DCX + neurons in the brains of infants to 100 year-old individuals. Layer II DCX + neurons occurred throughout the cerebrum in the infants/toddlers, mainly in the temporal lobe in the adolescents and adults, and only in the temporal cortex surrounding the amygdala in the elderly. Amygdalar DCX + neurons occurred in all age groups, localized primarily to the PLN, and reduced in number with age. The small-sized DCX + neurons were unipolar or bipolar, and formed migratory chains extending tangentially, obliquely and inwardly in layers I-III in the cortex, and from the PLN to other nuclei in the amygdala. Morphologically mature-looking neurons were lightly labeled and co-expressed the neuron-speci c nuclear antigen, glutamic acid decarboxylase and nicotinamide adenine dinucleotide phosphate-diaphorase. Taken together, we consider that the layer II and amygdalar DCX + neurons form a slowly developing interneuron system that supports inhibitory network plasticity in the cerebrum in an age/region-dependent manner.

Spatial transcriptomic analysis of adult hippocampal neurogenesis in the human brain

“…Previous reports have shown expression of DCX in non-neurogenic regions, such as the human amygdala 20,[36][37][38] and cerebral cortex 36 . These findings raise concerns regarding the validity of DCX as an appropriate proxy for adult brain neurogenesis.…”

“…These findings raise concerns regarding the validity of DCX as an appropriate proxy for adult brain neurogenesis. To further confirm DCX expression in nonneurogenic regions 20,[36][37][38] , we first spatially mapped the expression of DCX and PROX1 onto publicly available spatial genomic data of dorsolateral prefrontal cortex (DLPFC) sections 39 . DCX expression was visible in a few sub-spots in all four DLPFC sections, whereas PROX1 is mainly expressed in sub-spots located in the cluster annotated as white matter (Fig.…”

Age-related changes in the primary auditory cortex of newborn, adults and aging bottlenose dolphins (Tursiops truncatus) are located in the upper cortical layers

“…Interestingly, the presence of these idle immature neurons at birth, which can activate later in life, would also alleviate the need for neuron number changes in the cortex, which do not seem to occur in other mammals 10.3389/fnana.2023.1330384 Frontiers in Neuroanatomy 10 frontiersin.org significantly. Doublecortin has been used to find evidence of these idle cells throughout the lifespan of rodents (Benedetti et al, 2023) and humans (Li et al, 2023). Further consideration could be taken regarding the presence of Doublecortin in cetaceans, as it could represent a key in brain plasticity (Bonfanti et al, 2023).…”

Neuroplasticity of children in autism spectrum disorder

“…Abnormalities in neuroplasticity have been found in brains of patients with ASD, potentially leading to abnormal neuronal connectivity and circuit formation, affecting information transmission and coordination between brain regions ( 5 ). This plasticity is a complex process with increased sensitivity during fetal and infant brain development and to a lesser extent during adolescence and adulthood ( 6 ). This review focuses on the important role of neuroplasticity in ASD in terms of genetics, environment, neural pathways, neuroinflammation, and immunity to inform the design, timing, and sequencing of neuromodulatory interventions for clinical research to enhance and optimize their translational application in childhood brain disorders.…”