The effect of hemorrhage on the development of the postnatal mouse cerebellum.

Recent studies have shown that hemorrhagic injury in the preterm cerebellum leads to long-term neurological sequelae, such as motor, affective, and cognitive dysfunction. How cerebellar hemorrhage (CBH) affects the development and function of the cerebellum is largely unknown. Our study focuses on developing a mouse model of CBH to determine the anatomical, behavioral, and molecular phenotypes resulting from a hemorrhagic insult to the developing cerebellum. To induce CBH in the postnatal mouse cerebellum, we injected bacterial collagenase, which breaks down surrounding blood vessel walls, into the fourth ventricle at postnatal day two. We found a reduction in cerebellar size during postnatal growth, a decrease in granule cells, and persistent neurobehavioural abnormalities similar to abnormalities reported in preterm infants with CBH. We further investigated the molecular pathways that may be perturbed due to postnatal CBH and found a significant upregulation of genes in the inflammatory and sonic hedgehog pathway. These results point to an activation of endogenous mechanisms of injury and neuroprotection in response to postnatal CBH. Our study provides a preclinical model of CBH that may be used to understand the pathophysiology of preterm CBH and for potential development of preventive therapies and treatments.

Bi-parental care contributes to sexually dimorphic neural cell genesis in the adult mammalian brain.

Early life events can modulate brain development to produce persistent physiological and behavioural phenotypes that are transmissible across generations. However, whether neural precursor cells are altered by early life events, to produce persistent and transmissible behavioural changes, is unknown. Here, we show that bi-parental care, in early life, increases neural cell genesis in the adult rodent brain in a sexually dimorphic manner. Bi-parentally raised male mice display enhanced adult dentate gyrus neurogenesis, which improves hippocampal neurogenesis-dependent learning and memory. Female mice display enhanced adult white matter oligodendrocyte production, which increases proficiency in bilateral motor coordination and preference for social investigation. Surprisingly, single parent-raised male and female offspring, whose fathers and mothers received bi-parental care, respectively, display a similar enhancement in adult neural cell genesis and phenotypic behaviour. Therefore, neural plasticity and behavioural effects due to bi-parental care persist throughout life and are transmitted to the next generation.

Paternal recognition of adult offspring mediated by newly generated CNS neurons.

In mammals, olfaction is often used to distinguish individuals on the basis of their unique odor types (genetically programmed body odors). Parental-offspring recognition behavior is mediated, in part, by learning and processing of different odor types and is crucial for reproductive success. Maternal recognition behavior and associated brain plasticity has been well characterized, but paternal recognition behavior and brain plasticity is poorly understood. We found that paternal-adult offspring recognition behavior in mice was dependent on postnatal offspring interaction and was associated with increased neurogenesis in the paternal olfactory bulb and hippocampus. Newly generated paternal olfactory interneurons were preferentially activated by adult offspring odors. Disrupting prolactin signaling abolished increased paternal neurogenesis and adult offspring recognition. Rescuing this neurogenesis restored recognition behavior. Thus, neurogenesis in the paternal brain may be involved in offspring recognition.

Identity crisis for adult periventricular neural stem cells: subventricular zone astrocytes, ependymal cells or both?

A population of neural stem cells (NSCs) resides adjacent to the lateral ventricles in the adult mammalian brain. Despite knowledge of their existence since the early 1990s, their identity remains controversial, with evidence suggesting that they may be ependymal cells, glial fibrillary acidic protein (GFAP)-expressing subventricular zone (SVZ) cells or several distinct NSC populations. This issue has major implications for the therapeutic use of NSCs as well as for the study and treatment of brain cancers. Recent studies have both shed light on the issue and added to the controversy.

Male pheromone-stimulated neurogenesis in the adult female brain: possible role in mating behavior.

The regulation of female reproductive behaviors may involve memories of male pheromone signatures, formed in part by neural circuitry involving the olfactory bulb and hippocampus. These neural structures are the principal sites of adult neurogenesis; however, previous studies point to their independent regulation by sensory and physiological stimuli. Here we report that the pheromones of dominant (but not subordinate) males stimulate neuronal production in both the olfactory bulb and hippocampus of female mice, which are independently mediated by prolactin and luteinizing hormone, respectively. Neurogenesis induced by dominant-male pheromones correlates with a female preference for dominant males over subordinate males, whereas blocking neurogenesis with the mitotic inhibitor cytosine arabinoside eliminated this preference. These results suggest that male pheromones are involved in regulating neurogenesis in both the olfactory bulb and hippocampus, which may be important for female reproductive success.