combined-mechanical-enzymatic-dissociation-mouse-brain-hippocampal

Combined Mechanical and Enzymatic Dissociation of Mouse Brain Hippocampal Tissue

This neural dissociation protocol (an adaptation of the protocol accompanying a commercial adult brain dissociation kit) optimizes tissue processing in ...

University of Arkansas for Medical Sciences

Astronauts traveling to Mars will be exposed to high levels of ionizing radiation upon leaving low-Earth orbit. During prolonged space travel, astronauts are exposed to galactic cosmic rays (GCRs) composed of protons; oxygen molecules; and high energy, high mass charged particles. Notably, oxygen molecules can travel through the shielding of spacecraft, potentially impacting 25% of the hippocampus. The aim of the current study was to assess whether O-particle radiation induced a behavioral deficit and histological changes in mice. Mice were sent to the National Aeronautics and Space Administration (NASA) Space Radiation Laboratory at Brookhaven National Laboratory and exposed to particulate O radiation at doses of 0 and 0.05 Gy. Nine months after irradiation, the mice were tested for novel object recognition and in the Y-maze, after which the animals were sacrificed. The brains were then dissected along the midsagittal plane for Golgi staining. Exposure to 0.05 Gy significantly impaired novel object recognition. However, short term memory and exploratory activity in the Y-maze were not affected. Micromorphometric analysis revealed significant decreases in mushroom spine density in the dentate gyrus and cornu Ammonis-1 and -3 of the hippocampus. Sholl analysis revealed a significant decrease in dendritic complexity in the dentate gyrus. The present data provide evidence that space radiation has deleterious effects on mature neurons associated with hippocampal learning and memory.

Long-Term Changes in Cognition and Physiology after Low-Dose O Irradiation.

Cranial and craniospinal irradiation are the oldest central nervous system prophylaxis treatments considered for pediatric patients with acute lymphoblastic leukemia (ALL). However, survivors of childhood ALL that received cranial radiotherapy are at increased risk for deficits in neurocognitive skills. The continuous and dynamic response of normal tissue after irradiation has been identified as one of the causative factors for cognitive changes after cranial radiation therapy. The aim of our study was to investigate the radiation effects on social behavior and neuronal morphology in the hippocampus of adult mice. Twenty-oneday-old male C57BL/6 mice were irradiated with the small-animal radiation research platform (SARRP). Animals were given a single 10-Gy dose of radiation of X-ray cranial radiation. One month following irradiation, animals underwent behavioral testing in the Three-Chamber Sociability paradigm. Radiation affected social discrimination during the third stage eliciting an inability to discriminate between the familiar and stranger mouse, while sham successfully spent more time exploring the novel stranger. Proteomic analysis revealed dysregulation of metabolic and signaling pathways associated with neurocognitive dysfunction such as mitochondrial dysfunction, Rac 1 signaling, and synaptogenesis signaling. We observed significant decreases in mushroom spine density in the Cornu Ammonis 2 of the hippocampus, which is associated with sociability processing.

Cranial irradiation impairs juvenile social memory and modulates hippocampal physiology.

Breast cancer is the most commonly diagnosed cancer among women and it is estimated that about 30% of newly diagnosed cancers in women will be breast cancers. While advancements in treating breast cancer have led to an average 5-year survival rate of 90%, many survivors experience cognitive impairments as a result of chemotherapy treatment. Doxorubicin, cyclophosphamide, and docetaxel (TAC) are commonly administered as breast cancer treatments; however, there are few studies that have tested the cognitive effects of TAC. In the current study, 12-week-old female C57BL/6 mice received 4 weekly intraperitoneal injections of either saline or a combination therapy of doxorubicin and cyclophosphamide followed by 4 weekly docetaxel injections. Four weeks after the last injection, mice were tested for hippocampus-dependent cognitive performance in the Y-maze and the Morris water maze. During Y-maze testing, mice exposed to TAC exhibited impairment. During the water maze assessment, all animals were able to locate the visible and hidden platform locations. However, mice that received the TAC presented with a significant impairment in spatial memory retention on the probe trial days. TAC treatment significantly decreases the dendritic complexity of arborization in the dentate gyrus region of the hippocampus. In addition, comparative proteomic analysis revealed downregulation of proteins within key metabolic and signaling pathways associated with cognitive dysfunction, such as oxidative phosphorylation, ephrin signaling, and calcium signaling.

Article	Year
Long-Term Changes in Cognition and Physiology after Low-Dose O Irradiation. International journal of molecular sciences\| PubMed ID: 30621014	2019
Cranial irradiation impairs juvenile social memory and modulates hippocampal physiology. Brain research\| PubMed ID: 32896524	2020
Cognitive impairment resulting from treatment with docetaxel, doxorubicin, and cyclophosphamide. Brain research\| PubMed ID: 33705788	2021

Fabio Ntagwabira

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