Alzheimer's disease (AD), a progressive neurodegenerative disorder characterized by memory loss and dementia, could be a consequence of the abnormalities of cortical milieu, such as oxidative stress, inflammation, and/or accompanied with the aggregation of β-amyloid. The majority of AD patients are sporadic, late-onset AD, which predominantly occurs over 65 years of age. Our results revealed that the ferrous amyloid buthionine (FAB)-infused sporadic AD-like model showed deficits in spatial learning and memory and with apparent loss of choline acetyltransferase (ChAT) expression in medial septal (MS) nucleus. In hippocampal CA1 region, the loss of pyramidal neurons was accompanied with cholinergic fiber loss and neuroinflammatory responses including glial reaction and enhanced expression of inducible nitric oxide synthase (iNOS). Surviving hippocampal CA1 pyramidal neurons showed the reduction of dendritic spines as well. Astaxanthin (ATX), a potent antioxidant, reported to improve the outcome of oxidative-stress-related diseases. The ATX treatment in FAB-infused rats decreased neuroinflammation and restored the ChAT + fibers in hippocampal CA1 region and the ChAT expression in MS nucleus. It also partly recovered the spine loss on hippocampal CA1 pyramidal neurons and ameliorated the behavioral deficits in AD-like rats. From these data, we believed that the ATX can be a potential option for slowing the progression of Alzheimer's disease.

Fetal alcohol spectrum disorder (FASD) caused by mother's exposure to alcohol during pregnancy is a congenital neurological disease of the fetus resulting in fetal developmental and intellectual disabilities, cognitive impairment, and coordination disorder. Excess oxidative stress and neuroinflammatory responses were an important factor in neuropathological changes in FASD. Astaxanthin (AST) was a potent antioxidant and anti-inflammatory carotenoid. Therefore, this study proposed to explore how AST treatment can ameliorate morphological changes in the hippocampus and cognitive impairment in FASD rats by reducing oxidative stress and neuroinflammation in the brain. An alcohol atomizer was used from postnatal day (P) 2 to P10 to induce the FASD rat model. They were treated with AST (10 mg/kg body weight/day, intraperitoneal injection) for 8 consecutive days starting at P53 and sacrificed at P60. FASD rats had growth retardation and facial dysmorphologies, excessive oxidative stress and neuroinflammation in the hippocampus, decreased choline acetyltransferase (ChAT) expression in MS nucleus, spine loss on hippocampal CA1 pyramidal neurons, and poor performance in spatial learning and memory and sensory-motor coordination. After AST treatment, oxidative stress, neuroinflammation, cholinergic system, excitatory synaptic structure and behavior of FASD rats improved. Therefore, our study provided evidence to support the proposal that AST could be considered to treat FASD.

Women are at a higher risk of cognitive impairments and Alzheimer’s disease (AD), particularly after the menopause, when the estrous cycle becomes irregular and diminishes. Numerous studies have shown that estrogen deficiency, especially estradiol (E2) deficiency, plays a key role in this phenomenon. Recently, a novel polymeric drug, hyaluronic acid–17β-estradiol conjugate (HA-E2), has been introduced for the delivery of E2 to brain tissues. Studies have indicated that HA-E2 crosses the blood–brain barrier (BBB) and facilitates a prolonged E2 release profile while lowering the risk of estrogen-supplement-related side effects. In this study, we used ovariohysterectomy (OHE) rats, a postmenopausal cognitive deficit model, to explore the effect of a 2-week HA-E2 treatment (210 ng/kg body weight, twice a week) on the cholinergic septo-hippocampal innervation system, synaptic transmission in hippocampal pyramidal neurons and cognitive improvements. Our study revealed an 11% rise in choline acetyltransferase (ChAT) expression in both the medial septal nucleus (MS nucleus) and the hippocampus, along with a 14–18% increase in dendritic spine density in hippocampal pyramidal neurons, following HA-E2 treatment in OHE rats. These enhancements prompted the recovery of cognitive functions such as spatial learning and memory. These findings suggest that HA-E2 may prevent and improve estrogen-deficiency-induced cognitive impairment and AD.

Women are at higher risk of cognitive impairment and Alzheimer’s disease (AD) after menopause when the estrous cycle becomes irregular and begins to taper off. Numerous studies have shown that estrogen deficiency, especially estradiol (E2), has been shown to play a key role in this phenomenon. Recently, a novel polymeric drug, hyaluronic acid-17β-Estradiol conjugate (HA-E2), has been developed which has the ability to cross the blood-brain barrier (BBB), facilitate a longer E2 release profile and lower risk of estrogen supplement related side effects. In this study, we used an ovariohysterectomy (OHE) rat model of postmenopausal cognitive deficits and explore whether HA-E2 treatment can improve the cholinergic septo-hippocampal innervation system, synaptic transmission in the hippocampal pyramidal neuron and cognitive impairment. Our results show that OHE rats after HA-E2 administration have increased expression of choline acetyltransferase (ChAT) in the medial septal nucleus (MS nucleus) and the hippocampus, increased spine density in hippocampal pyramidal neurons, and improved spatial learning and memory. Therefore, HA-E2 has great potential as a new novel class of drugs for estrogen-deficiency-induced cognitive impairment and AD.