Inadequate Expression and Activation of Mineralocorticoid Receptor Aggravates Spatial Memory Impairment after Traumatic Brain Injury

The Dose-dependent Dual Effects of Corticosterone on Spatial Memory Ability After Traumatic Brain Injury Are Mediated by Two Corticosteroid Receptor Systems

“…The nuclear translocation of receptors is an important parameter for assessing the activation level of MR and GR. Our recent studies have proved that CORT insu ciency, inadequate activation of MR and imbalance of MR/GR are important factors leading to apoptosis of hippocampal neurons in the acute phase after TBI [20]. In this study, we showed that nuclear MR and the ratio of MR/GR were signi cantly (P 0.05) reduced in the ipsilateral hippocampus after TBI.…”

“…MWM test was used to test the spatial memory ability in this study. Rats (n=24 per group) were trained using MWM before injury according to the protocol described before [20]. Each rat received 4 trials per day for 5 consecutive days (8-4 days before CCI) to nd the platform submerged below the water (20±2°C, with nontoxic black ink).…”

“…Excessive activation of GR by MP and DEX increased the neuronal apoptosis by activating GR in hippocampus and hypothalamus, aggravated spatial memory and stress dysfunction, and increased the mortality. In contrast, low-dose corticosterone (CORT) replacement restored the plasma CORT, re lled MR, and promoted the survival of neurons, but the dose-dependent effects of CORT and the receptor-mediated downstream mechanisms remain unclear [19][20][21]. cAMP-responsive element-binding protein (CREB) and several intracellular pathways have been demonstrated to be crucial for regulating the apoptotic-related proteins and neuronal apoptosis after TBI.…”

Mineralocorticoid receptor antagonist‐mediated cognitive improvement in a mouse model of Alzheimer's type: possible involvement of BDNF‐H2S‐Nrf2 signaling

“…However, studies have shown their expanding spectrum in a number of diseases including diabetic nephropathy [5], treatment‐resistant hypertension [6]. There have been studies showing that activation of mineralocorticoid receptors may be associated with impairment in memory [16], and blockade of these receptors may be beneficial in memory [17]. However, it is the first study showing the memory improvement actions of spironolactone and eplerenone in Aβ‐induced cognitive impairment of Alzheimer's type.…”

“…These receptors are also abundantly expressed on the immune cells, including microglia, and their role in the induction of neuroinflammation is also well documented [15]. Furthermore, studies have shown the usefulness of mineralocorticoid receptor blockers in improving memory functions [16,17]. However, their role and mechanisms in dementia of Alzheimer's type are not explored.…”