Effect Of Chronic Unpredictable Mild Stress On BDNF Expression In Sub Regions Of Brain In Different Aged Rat

Stress is a general responsive state of the body including mental, neuroendocrine and immune system changes when organism is threatened by great change from environment. Hypothalamic-pituitary-adrenal (HPA) axis and locus ceruleus adrenergic nerve suprarenal medulla system (LC-AN-SMS) play important roles in response to stress, and Hypothalamic-pituitary-thyroid (HPT) axis, Hypothalamic-pituitary-gonad (HPG) axis also can be involved in stress responses.Persistent hyperfunction of HPA axis and high level of glucocorticoid (GCs) are the pathological foundation of the Chronic Stress. Sub areas in the central nervous system (CNS) such as hippocampus, prefrontal cortex (PFC) and striatum which related closely with cognition, emotion and behavior are the major attacked targets of GCs for their high glucocorticoid receptors (GR) expression. Chronic stress can cause degeneration and cellular necrosis of pyramidal neurons in hippocampal CA3 and gyrus dentatus subfield, reduce the volume of PFC as well as decrease the levels of monoamine in striatum. Some evidences have indicated that depression induced by chronic stress is associated with reduced volumes in the hippocampus, ventral striatum and PFC.Recent studies have indicated that physiological and emotional stresses have a relationship with brain derived neurotrophic factor (BDNF). As a member of the family of neurotrophins (NTs), BDNF exhibits diverse important effects such as neuronal survival and maturation, neurogenesis, synaptogenesis, cell differentiation and synaptic plasticity in a variety of CNS neurons including cholinergic neuron, dopaminergic neuron, motor neuron and aminobutyric acid neuron. Meanwhile, BDNF also shows an important protective effect during the stress. There is a growing body of evidence demonstrating that chronic stress can suppress the expression of BDNF in hippocampus CA3 and PFC. The reactivity and tolerance of body to stress are related to aging. Researches have found that rodents aging animals had a higher level of serum corticotrophin releasing hormone(CRH), adrenocorticotropic hormone (ACTH) and GCs and they were more supersensitive to the chronic stress.Using chronic unpredictable mild stress(CUMS), the present study observed the behavior and BDNF expression in CA3 sub region and dentate gyrus of hippocampus, striatum and PFC in 72 different aged (2 month old and 15 month old) Wistar rats. The results of this experiment are as follows:1. Compared with the control groups, the stress groups of young and aged rats displayed time delay in central square, less square crossing, vertical movement and grooming on 21^st day of stress and 7^th day after stress period. Aged stress animals had more remarkable changes in central square, square crossing, vertical movement and grooming than the young stress group.2. The stress rats showed obviously decreased tendency in sucrose consumption and sucrose preference on 21^st day of stress and 7^th day after stress period compared with the control groups. The total water consumption demonstrated no obvious change between the stress groups and control groups. Meanwhile, the aged stress group exhibits more lower sucrose consumption and sucrose preference on 21^st day of stress and 7^th day after stress period than the young stress group.3. The stress groups displayed obviously morphologic changes such as intercellular space broaden, disordered cell arrange, neurons degenerative atrophy and cellular necrosis in sub regions of brain on 21^st day of stress and 7^th day after stress period. Contrasted with the young stress group, the aged stress group showed more cell atrophy and cellular necrosis in every sub regions on 21^st day of stress and 7^th day after stress period. 4. The stress rats had significant lower BDNF expression in sub region of brain than the control groups on 21^st day of stress and 7^th day after stress period, the aged stress rats showed lower BDNF expression in every sub area than the young stress rats at every testing time.Conclusion:1. CUMS could induce different extent damage of young and aged rat, the aged rat had more serious abnormal of behavior under stress. It indicates that aging is one of the important influence factors in stress.2. CUMS could decrease the sucrose consumption and sucrose preference in different young and aged rats, the aged rats had a lower sucrose consumption and sucrose preference than the young rats. It shows that chronic stress can induce animals to loss the interest and the aged animals had more significant losses of interest.3. CUMS could cause the morphology changes such as intercellular space broaden, disordered cell arrange, neurons degenerative atrophy and cellular necrosis in hippocampal CA3 and gyrus dentatus subfield, PFC and striatum. The aged rats showed more seriously cell atrophy and cellular necrosis in every sub regions than the young rats.4. CUMS could induce significant reduction of BDNF expression in hippocampal CA3 and gyrus dentatus subfield, PFC and striatum. The aged rats had much lower BDNF expression in every sub area than the young rats.