Niemann‐Pick type C (NPC) disease is an autosomal recessive lysosomal storage disorder affecting mostly children, causing progressive neurological deterioration and death. NPC disease is caused by a mutation in either the NPC1 or NPC2 gene, leading to a loss of functional NPC1 or NPC2 protein. These proteins play a role in lipid egress from late endosomes and lysosomes, a deficiency in either results in intracellular accumulation of unesterified cholesterol and gangliosides. Storage is prominent in neurons, influencing cellular pathology, such as growth of ectopic dendrites on pyramidal neurons. This aberrant growth of dendrites following normal dendritogenesis has been documented in several lysosomal diseases characterized by ganglioside storage. Until recently, the visualization of this process depended on the Golgi method. New techniques, such as endogenous expression of fluorescent proteins, provide an in‐depth analysis of neuronal structure. We hypothesized that the accumulation of gangliosides in NPC disease will cause an initial enhancement of dendritogenesis along with ectopic dendrite growth followed by a subsequent degeneration of dendritic trees later in disease. Subsequently, we generated a transgenic Npc1 murine mouse model whose layer V cortical pyramidal neurons express yellow fluorescent protein (YFP) to investigate the dendritic abnormalities of NPC disease relative to lysosomal storage. Confocal imaging and Neurolucida Software are being used to image YFP+ pyramidal neurons, which will be analyzed for changes in dendritic size, complexity and pathological state.

The mu opioid receptor (MOR) has a significant role in fear conditioning and extinction learning. Communication between amygdala, periaqueductal gray (PAG) and medial prefrontal cortex (mPFC) regulates fear conditioning and extinction. Fear conditioned female rats during the metaestrus (M, low hormones) stage of the estrous cycle, showed impaired extinction while rats during the proestrus (P, high hormones) stage showed normal extinction learning. We aim to elucidate how opioid modulators alter MOR expression during fear conditioning and extinction in both sexes. Female rats on M or P stages and males rats underwent auditory fear conditioning and immediately received MOR agonist morphine, or antagonist naloxone or saline. The next day rats received extinction trials. Western blots were used to measure MOR expression. In the PAG, female rats showed no change with either treatment. In male rats morphine produced an increase in MOR expression while naloxone had an opposite effect. In the PFC, morphine during P decreased MOR expression while naloxone had no effect. Increased MOR expression was observed in the amygdala of male rats after either morphine or naloxone treatments, while in females an increase in MOR was only observed during P. Our data portraits sex differences in MOR expression in the fear circuitry, which might be responsible for the persistence of fear responses during low ovarian hormone stages. Grant Funding Source: Supported by Molecular and Genomics core RR003050, Behavioral Core Facilities MD007579 , HPD335698 Nova Southeastern University to Edwin Santini and Dinah Ramos‐Ortolaza

Cocaine is a highly addictive psychostimulant drug with a high relapse rate. Studies have shown that women have greater subjective responses to cocaine depending on the hormonal phase they are in, making them more susceptible to addiction. Literature shows that sex hormones can modulate the activities of Brain‐Derived Neurotrophic Factor (BDNF). BDNF modulates the growth and survival of neurons in areas such as the nucleus accumbens (NAc) and prefrontal cortex, specifically the pre‐limbic cortex (PL). However, it is still unknown how hormonal stages influence the expression of BDNF in the different phases of cocaine addiction development: self‐administration, extinction and reinstatement. We hypothesized that the expression of BDNF in the NAc and PL varies depending on the hormonal stage, as well as the stage in the development of cocaine addiction. To determine this, female adult rats were subjected to 12 sessions of short‐access self‐administration of cocaine, 16 sessions of extinction and a session of cue‐primed reinstatement. Tissue from the PL and NAc were extracted to compare the expression of BDNF after each phase of cocaine addiction. Preliminary data suggests that BDNF decreases in the NAc during low‐hormonal phases (Diestrus and Metestrus), while it increases during high‐hormonal phases (Estrus and Proestrus). In addition, BDNF protein levels seem to be elevated in the prelimbic cortex after cue‐primed reinstatement, but further analysis is required to confirm this observation. These findings suggest that BDNF expression depends on the phase of cocaine addiction and the estrous cycle in female rats. Support or Funding Information Funding was received from the following sources: UPR PRISE Program: #R25GM096955; Start up funds from Ponce Research Institute; Rise Program: NIH‐NIGMS #2R25GM082406; B.R.A.I.N. and M.A.G.I.C. Core: NIM‐HD MD007579.