Stress Hormones,the Brain

andBehavior

What is stress?

What is stress?It is “a real or interpreted threatto the physiological orpsychological integrity of anindividual that results inphysiological and/or behavioralresponses. In biomedicine,stress often refers to situationsin which adrenal glucocorticoidsand catecholamines are elevated because of an experience.”

McEwen, B. (2000) In G. Fink(Ed.) Encyclopedia of Stress,Vol. 3. San Diego: Academic Press.

What is stress?

stress stimulus?“I’m under a lot of stress.”

subjective experience?“I’m feeling stressed out.”depression

deviation from homeostasis?

hunger, thirst, fatigue

endocrine response?circulating stress hormones

Two types of stress1. Systemic stress

physiological threat

2. Processive stress potential or eventual threat

In adults, responses to processive, but not systemic,stress is blocked by lesions ofthe hippocampus

Systemic stress is also referred to asphysiological stress, and processivestress is oten referred to as psychological stress

Hypothalamus

Adenohypophysis

Adrenal Cortex

Target tissues

Control ofStress Hormones

IndirectLoop

ShortLoop

DirectLoop

CRF(aka CRH)

Corticotrophin(aka ACTH)

Cortisol or Corticosterone

neural inputs(limbic system)

This is usually referred to as the “HPA axis,”but is now often called the “LHPA axis.”

Paraventricular Nucleus

(CRF)

As withthyroid hormones and sex hormones

One can ask, are there

“organizational effects”and

“activational effects”?

Stress hyporesponsive period

Meany, M.J., Sapolsky R.M. * McEwen, B.S. (1985) The development of the glucocorticoid receptor system in the rat limbic brain: I. Ontogeny and autoregulation. Developmental Brain Research, 18, 159-164.

Avishai-Eliner, S., Brunson, K.L., Sandman, C.A.& Baram, T.Z. (2002) Stressed-out, or in (utero)?Trends Neurosci., 25, 518-524.

CRH mRNACRH

mRNA

HippocampusLow concentration of bioactive receptors

HypothalamusDiminished CRF content:

potentially reduced CRF during stress

PituitaryDiminished ACTH content

Adult concentrations of bioactive receptorsPaucity of AUX receptors (CBG)

Adrenal CortexInvolution of the fetal zone

Neonatal SHRP

Little impact of CORT on hippocampalfunction, thus diminution of inhibitoryfeedback signal to hypothalamic CRFsystem. Basal adrenocortical activityis unsuppressible.

Attenuated CRF signal to the pituitaryduring stress

Exaggerated impact of CORT on pituitaryfunction due to heavy nuclear uptake ofCORT. The pituitary, already limited inits function, is desensitized to the limitedCRF signal.

Limited secretory capacity

Stress hyporesponsive period

Meany, M.J., Sapolsky R.M. * McEwen, B.S. (1985) The development of the glucocorticoid receptor system in the rat limbic brain: I. Ontogeny and autoregulation. Developmental Brain Research, 18, 159-164.

Levine, S. (2005) Developmental determinantsof sensitivity and resistance to stress. Psychoneuroendocrinology, 30, 939-946.

Knackstedt, M.K., Hamelmann, E. & Arck, P.C.(2005) Mothers in stress: Consequences for theoffspring. Am. J. Reprod. Immunol., 54, 63-69.

Knackstedt, M.K., Hamelmann, E. & Arck, P.C.(2005) Mothers in stress: Consequences for the offspring. Am. J. Reprod. Immunol., 54, 63-69.

Maternal stress perception leads to prolonged activation of the HPA axis within the maternal organism. This induces increased levels of CRH. CRH suppress es progesterone secretion and therefore diminishes the levels of progesterone induced blocking factor (PIBF), an important immune modulator during pregnancy. CRH also leads to an augmentation of circulation glucocorticoids. This leads to a shift from Th2 to a Th1 immunity resulting in increased expression of TNF-a at the feto–maternal interface. Elevated expression of TNF-α is associated with increased apoptosis in the placenta as well as priming the fetal immune system. Most likely, high levels of Th1 cytokines at the feto–maternal interface evoke counteracting mechanism leading to immunosuppression and a predisposition of the immune system towards atopic disease. Augmented levels of glucocorticoids have a negative feedback on growth hormone release leading to fetal growth restriction. Low birth weight in turn predisposes to type II diabetes,

(Tumor Necrosis Factor)

Stress increases placental CRH to fetus; CRH excitatory inputs to hippocampal neurons facilitates synaptic development in low levels but is excitotoxic at high levels

Avishai-Eliner, S., Brunson, K.L., Sandman, C.A. & Baram, T.Z.(2002) Stressed-out, or in (utero)? Trends Neurosci., 25, 518-524.

activity-dependent modulation of neuronalgrowth and differentiation by glucocorticoids(membrane effects)

Avishai-Eliner, S., Brunson, K.L., Sandman, C.A.& Baram, T.Z. (2002) Stressed-out, or in (utero)?Trends Neurosci., 25, 518-524.

Also, maternal stress can cause feedback inhibition of testosterone secretion from fetal testes;

less masculinized andless defeminized males

Altered development of the hippocampus results inaltered responses to stressfulstimuli, especially processive (psychological) stressors

cholesterol