Neuronal activity can modify Alzheimer’s disease pathology. Overexcitation of neurons can facilitate disease progression whereas the induction of cortical gamma oscillations can reduce amyloid load and improve cognitive functions in mouse models. Although previous studies have induced cortical gamma oscillations by either optogenetic activation of cortical parvalbumin-positive (PV+) neurons or sensory stimuli, it is still unclear whether other approaches to induce gamma oscillations can also be beneficial. Here we show that optogenetic activation of PV+ neurons in the basal forebrain (BF) increases amyloid burden, rather than reducing it. We applied 40 Hz optical stimulation in the BF by expressing channelrhodopsin-2 (ChR2) in PV+ neurons of 5xFAD mice. After 1-h induction of cortical gamma oscillations over three days, we observed the increase in the concentration of amyloid-β42 in the frontal cortical region, but not amyloid-β40. Amyloid plaques were accumulated more in the medial prefrontal cortex and the septal nuclei, both of which are targets of BF PV+ neurons. These results suggest that beneficial effects of cortical gamma oscillations on Alzheimer’s disease pathology can depend on the induction mechanisms of cortical gamma oscillations.
This study evaluated the beneficial impact of daily oral administration with date palm pollen (DPP) on the reproductive efficiency, parameters of blood, ovarian activity and reproductive hormonal profiles in NZW rabbit does. Does (n=60) were divided into 3 treatments (20 in each) administered with 0, 250 and 500 mg DPP/doe dissolved in distilled water (2 ml) respectively, for 35 d premating. Does were naturally mated with adult NZW bucks at the termination of treatment period (35 d). Both levels of DPP significantly increased pregnancy and viability rates, and litter characteristic at birth and weaning as compared to control. Oral treatment with both DPP levels significantly increased Hb, RBCs and hematocrit, serum total proteins, albumin, globulin and glucose and high-density lipoprotein, while significantly decreased WBCs serum total cholesterol, triglycerides, and lowdensity lipoprotein compared with control. Does receive both DPP levels had significantly improved kidney and liver functions, antioxidants capacity and immune response markers than the control group. Both levels of DPP showed significantly (P<0.05) remarkable improvement of estrogen, progesterone and prolactin of rabbit does comparing with control. Rate of ovulation and embryo quality and quality were increased (P<0.05) by DPP levels comparing with control group. The data showed that orally administration of DPP may help in improving the reproductive efficiency of does via adjusting the hematological and metabolites of blood, reducing lipid profile and peroxidation, improving the antioxidant capacity and immunity, and improving the ovarian activity and embryo quality.Rabbits, date palm pollen, reproductive efficiency, antioxidants, immunity
Neuronal activity can modify Alzheimer's disease pathology. Although overexcitation of neurons can facilitate disease progression, the induction of cortical gamma oscillations can reduce amyloid load and improve cognitive functions in mouse models. These beneficial effects of gamma oscillations can be caused by either optogenetic activation of cortical parvalbumin-positive (PV+) neurons or 40 Hz repetitive sensory stimuli. However, given the fact that cortical gamma oscillations can be induced by multiple mechanisms, it is still unclear whether other approaches to induce gamma oscillations can also be beneficial. Here we show that optogenetic activation of PV+ neurons in the basal forebrain (BF) increases amyloid burden, rather than reducing it. We applied 40 Hz optical stimulation in the BF of 5xFAD mice by expressing channelrhodopsin-2 (ChR2) in PV+ neurons. After one-hour induction of cortical gamma oscillations over three days, we observed the increase in the concentration of amyloid-β42 in the frontal cortical region, but not amyloid-β40. The density of amyloid plaques also increased in the medial prefrontal cortex and the septal nuclei, both of which are targets of BF PV+ neurons. These results suggest that effects of cortical gamma oscillations on Alzheimer's disease pathology can be bidirectional depending on their induction mechanisms. Significance StatementAlzheimer's disease (AD) is the most common cause of dementia. Although numerous molecular targets have been identified, the development of treatment is still a challenge. Accumulating evidence shows that artificial control of neuronal activity can modify AD pathology. In particular, the induction of cortical gamma (~40 Hz) oscillations can ameliorate AD pathology and improve cognitive functions. Here we show that optogenetic activation of parvalbumin-positive (PV+) neurons in the basal forebrain (BF) has opposite effects. By expressing channelrhodopsin-2 (ChR2) in PV+ neurons of an AD mouse model and optically stimulating BF PV+ neurons, we induced gamma oscillations Gamma oscillations and AD pathology 2 and found increased amyloid burden. These results imply that AD pathology can be modified bidirectionally depending on induction mechanisms of gamma oscillations.
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