Glyphosate exposure induces synaptic impairment in hippocampal neurons and cognitive deficits in developing rats.

Glyphosate is the active ingredient of several widely used herbicide formulations. Studies based on Glyphosate exposure in different experimental models have suggested that the nervous system represented a key target for its toxicity. Previously, we demonstrated that exposure to glyphosate during gestation induces deficits on behavioral and cognitive function in rats. The aim of the present work was to examine whether cognitive dysfunction induced by Glyphosate was connected to changes on synapse formation and maturation. To understand how glyphosate affects synaptic assembly, we performed in vitro assays on cultured hippocampal neurons that were exposed to the herbicide (0.5 or 1 mg/mL) for 5 or 10 days. Biochemical and immunocytochemical approaches revealed that Glyphosate treated neurons showed a decrease on dendritic complexity and synaptic spine formation and maturation. Moreover, results indicated that Glyphosate decreased synapse formation in hippocampal neurons. To evaluate these effects in vivo, pup rats were treated with 35 or 70 mg/kg of Glyphosate from PND 7 to PND 27, every 48 h. Results indicated that Glyphosate postnatal exposure induced cognitive impairments, since recognition and spatial memory were altered. To go further, we evaluated synaptic protein expression and synaptic organization in hippocampus. Images revealed that Glyphosate treatment downregulates synapsin-1, PSD-95, and CaMKII expression, and also decreased PSD-95 clustering in hippocampus. Taken together, these findings demonstrate for the first time that Glyphosate exposure affects synaptic assembly and reduced synaptic protein expression in hippocampus and that likely triggers the impairment of cognitive function and neuronal connectivity.

Antagonistic Relationship Between VEP Potentiation and Gamma Power in Visual Snow Syndrome.

OBJECTIVE: Using a "double-pulse" adaptation paradigm, in which two stimuli are presented in quick succession, this study examines the neural mechanisms underlying potentiation of the visual evoked potential (VEP) in visual snow syndrome. BACKGROUND: Visual snow is a persistent visual disturbance characterized by rapid flickering dots throughout the visual field. Like the related condition of migraine with aura, visual snow has been hypothesized to arise from abnormal neuronal responsiveness, as demonstrated by a lack of typical VEP habituation to repeated visual stimulation. Yet the exact neural mechanisms underlying this effect remain unclear. Previous "double-pulse" experiments suggest that typical VEP habituation reflects disruptive gamma-band (50-70 Hz) neural oscillations, possibly driven by inhibitory interneurons. Given that migraine has been associated with reduced cortical inhibition, we propose here that visual snow may likewise reflect diminished inhibitory activity, resulting in decreased gamma power following initial visual stimulation and concomitant potentiation of the subsequent VEP response. METHODS: We compared VEP responses to double-pulse adaptation in a 22-year-old man with a 2-year history of visual snow versus a group of age- and gender-matched controls (N = 5). The patient does not have a comorbid diagnosis of episodic migraine or migraine with aura, and controls had no personal or family history of migraine. RESULTS: In contrast to the pattern of habituation observed in controls, visual snow was associated with persistent potentiation of the VEP response. Consistent with our predictions, time-frequency analysis revealed reduced gamma-band power following the initial stimulus in visual snow relative to controls. CONCLUSIONS: These results support an antagonistic interplay between gamma power and rapid neural adaptation, shedding new light on the neural mechanisms of VEP potentiation in visual snow.