An Examination of Hippocampal Microglia and Anxiety Behavior after Chronic Peri-adolescent Asthma

Open Access
Author:
Schopf, Kerri Jean
Area of Honors:
Biology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Sonia Cavigelli, Thesis Supervisor
  • James Marden, Honors Advisor
Keywords:
  • microglia
  • behavior
  • hippocampus
  • asthma
  • anxiety
  • adolescence
  • asthma and anxiety
  • HDM
  • allergic asthma
Abstract:
Allergic asthma is a chronic immunological disease that affects over 22 million people in the U.S including 9% of adolescents. Importantly, adolescence is a period of substantial neurological development and coincides with asthma development which could have implications on the comorbidity of asthma with anxiety, depression and behavioral disorders. The hippocampus, a part of the brain implicated in mental health function, has a high density of microglia. These are resident immune cells of the brain that can become activated by peripheral immune challenges such as allergens, and have been implicated in mental health processes. In the current study, we determined whether peripheral asthma symptoms (airway inflammation, labored breathing) during development led to increased microglial activation in the hippocampus. In a mouse model, we used house dust mite extract, the most common human aeroallergen, and methacholine, a muscarinic receptor agonist, to induce airway inflammation and labored breathing, respectively. Hippocampal samples were collected at 0, 1, 2, 4, 8, and 24 hours after final asthma inductions on postnatal day 56 and slices were stained for Iba1, a microglia marker. CD11b, an eosinophil marker, and CCR3, a receptor expressed on microglia, expression were measured with reverse transcriptase polymerase chain reaction (rtPCR). Results indicate that there was a non-significant trend toward a greater number of microglia in the hippocampus of allergen-treated mice, and that CD11b and CCR3 genes were upregulated in allergen- and allergen- plus methacholine-treated mice. In addition, one cohort of mice was tested on the elevated plus maze, and data indicate that methacholine-induced labored breathing also caused increased anxiety-like behavior. These data indicate an asthma-anxiety comorbidity in a mouse model, but did not strongly support the role of microglia in the process. A larger sample size could elucidate a role of microglia in further studies.