Effects of restraint stress and betaxolol administration on G proteins expression in the rat hippocampus

Stres jest istotnym czynnikiem w patogenezie wielu chorób. Podczas odpowiedzi na stres aktywowany jest między innymi hipokamp, w obrębie którego dochodzi do zmian plastycznych. Nieznane są dokładne mechanizmy molekularne odpowiedzialne za ich powstawanie. W poniższej pracy określano udział białek G i receptora β1 adrenergicznego w reakcji na stres. Szczury szczepu Wistar były poddawane jednokrotnemu lub wielokrotnemu stresowi unieruchomienia i dekapitowane 24h po ostatniej sesji stresowania. Cześć zwierząt otrzymywała iniekcje antagonisty receptora β1-adrenergicznego - betaksolol (5mg/kg), który miał odwrócić skutki działania stresu. Poziom białek Gαq, Gα11, Gα12, RhoA, RhoB, RhoC i Rac1/2/3 w hipokampie był oznaczany metodą Western Blot.Wielokrotny stres unieruchomienia istotnie podwyższał ekspresję białka RhoA . Jednokrotny stres unieruchomienia powodował tendencję do obniżenia poziomu białka Gαq. W obu przypadkach betaksolol odwracał ten efekt. Zaobserwowano również tendencję do wzrostu ekspresji białka RhoB po wielokrotnym stresowaniu i jednoczesnym podawaniu betaksololu w drugim tygodniu procedury. Nie odnotowano istotnych zmian w poziomie pozostałych badanych białek.Otrzymane wyniki sugerują zaangażowanie powyższych białek i receptora β1-adrenergicznego w odpowiedzi komórek hipokampa na działanie stresu. Przeprowadzone badania przyczyniły się do lepszego poznania mechanizmu powstawania zmian indukowanych stresem i możliwości ich farmakologicznego odwrócenia.Stress is an important factor in the pathogenesis of many diseases. During stress response, the hippocampus is activated among others and this structure undergoes plastic modifications. Molecular mechanisms underlying this process are not well known. The following study determines involvement of β1-adrenergic receptor and G proteins in the response to stress. Male Wistar rats were restraint once or for 14 days and decapitated 24 hours after last stress session. Part of the animals received injections of β1-adrenoreceptor antagonist - betaxolol (5mg/kg) to reverse the effects of stress. Gαq, Gα11, Gα12, RhoA, RhoB, RhoC and Rac1/2/3 protein levels in hippocampus were determined by Western blot analysis.Chronic restraint stress significantly increased the expression of RhoA protein. A single restraint stress tends to reduce Gαq protein level. Betaxolol reverse this effect in both cases. There was also a tendency to increase RhoB protein level after chronic restraint stress and betaxolol co-administration in the second week of the procedure. No significant changes in the levels of other tested proteins were observed.The results suggest the involvement of these proteins and β1 adrenergic receptor in the cellular response to stress in hippocampus. The study contributed to a better understanding of the mechanisms underlying stress-induced changes and their possible pharmacological reversal

Postnatal and Adult Neurogenesis in Mammals, Including Marsupials

In mammals, neurogenesis occurs during both embryonic and postnatal development. In eutherians, most brain structures develop embryonically; conversely, in marsupials, a number of brain structures develop after birth. The exception is the generation of granule cells in the dentate gyrus, olfactory bulb, and cerebellum of eutherian species. The formation of these structures starts during embryogenesis and continues postnatally. In both eutherians and marsupials, neurogenesis continues in the subventricular zone of the lateral ventricle (SVZ) and the dentate gyrus of the hippocampal formation throughout life. The majority of proliferated cells from the SVZ migrate to the olfactory bulb, whereas, in the dentate gyrus, cells reside within this structure after division and differentiation into neurons. A key aim of this review is to evaluate advances in understanding developmental neurogenesis that occurs postnatally in both marsupials and eutherians, with a particular emphasis on the generation of granule cells during the formation of the olfactory bulb, dentate gyrus, and cerebellum. We debate the significance of immature neurons in the piriform cortex of young mammals. We also synthesize the knowledge of adult neurogenesis in the olfactory bulb and the dentate gyrus of marsupials by considering whether adult-born neurons are essential for the functioning of a given area

Effects of Brain Size on Adult Neurogenesis in Shrews

Shrews are small animals found in many different habitats. Like other mammals, adult neurogenesis occurs in the subventricular zone of the lateral ventricle (SVZ) and the dentate gyrus (DG) of the hippocampal formation. We asked whether the number of new generated cells in shrews depends on their brain size. We examined Crocidura russula and Neomys fodiens, weighing 10–22 g, and Crocidura olivieri and Suncus murinus that weigh three times more. We found that the density of proliferated cells in the SVZ was approximately at the same level in all species. These cells migrated from the SVZ through the rostral migratory stream to the olfactory bulb (OB). In this pathway, a low level of neurogenesis occurred in C. olivieri compared to three other species of shrews. In the DG, the rate of adult neurogenesis was regulated differently. Specifically, the lowest density of newly generated neurons was observed in C. russula, which had a substantial number of new neurons in the OB compared with C. olivieri. We suggest that the number of newly generated neurons in an adult shrew’s brain is independent of the brain size, and molecular mechanisms of neurogenesis appeared to be different in two neurogenic structures

Aged Opossums Show Alterations in Spatial Learning Behavior and Reduced Neurogenesis in the Dentate Gyrus

In many mammalian species including opossums, adult neurogenesis, the function of which is not completely understood, declines with aging. Aging also causes impairment of cognition. To understand whether new neurons contribute to learning and memory, we performed experiments on young and aged laboratory opossums, Monodelphis domestica, and examined the association between spatial memory using the Morris water maze test and the rate of adult neurogenesis in the dentate gyrus (DG). Modification of this test allowed us to assess how both young and aged opossums learn and remember the location of the platform in the water maze. We found that both young and aged opossums were motivated to perform this task. However, aged opossums needed more time to achieve the test than young opossums. Classical parameters measuring spatial learning in a water maze during a probe test showed that young opossums spent more time in the platform zone crossing it more often than aged opossums. Additionally, hippocampal neurogenesis was lower in the aged opossums than in the young animals but new neurons were still generated in the DG of aged opossums. Our data revealed individual differences in the levels of doublecortin in relation to memory performance across aged opossums. These differences were correlated with distinct behaviors, particularly, aged opossums with high levels of DCX achieved high performance levels in the water maze task. We, therefore suggest that new neurons in the DG of Monodelphis opossums contribute to learning and memory