Hair Loss

eurosci. 1992 May;12(5):1896-905.

On the role of nerve growth factor in the development of myelinated nociceptors.
Lewin GR, et al

We have previously demonstrated that administration of antisera against NGF (anti-NGF) can have profound effects on developing primary afferents (Ritter et al., 1991). Chronic administration of anti-NGF to rats beginning on the day of birth results in a severe depletion of cutaneous A delta high-threshold mechanoreceptors (HTMRs) from the sural nerve. Here we have carried out further experiments in order to define the period of time over which this change in the cutaneous afferent population can be produced, and to investigate a possible mechanism for the change. Treatment with anti-NGF from postnatal day (PND) 0-14 resulted in a depletion of cutaneous A delta HTMRs from the sural nerve and also a 20% loss of sensory neurons. However, treatment from PND 2-14 produced an identical deficit of HTMRs without any accompanying cell death. Thus, the depletion of cutaneous A delta HTMRs can be achieved in the absence of cell death induced by anti-NGF treatment. snip.. This critical period, PND 4-11, corresponds to a period of anatomical change in the innervation of the skin, from epidermal innervation to primarily dermal innervation. In every case where anti-NGF treatment reduced the proportion of HTMRs, there was a reciprocal increase in the proportion of sensitive A delta hair follicle (D-hair) afferents. We hypothesize that in the absence of NGF, developing cutaneous A delta HTMRs do not die but innervate novel targets in the dermis and become D-hair afferents instead.

The concept that electronically activated species (free radicals and the like) have a messenger role is called Redox signaling. Redox signaling likely plays a key role in regulating the hair loss and hair regrowth cycle, as well as in mediating pattern balding itself.

Our studies demonstrate that the death of hair follicles involves distinct patterns of expression of active caspases. Active caspase 8, an initiator of the death receptor pathway, was predominately found in the isthmic and upper lower portion of the shaft. This pattern of expression suggests that the death receptor pathway is activated during hair renewal and is initiated by toxic substances that bind to death receptors, i.e., TNF-alpha. Interestingly, activated caspase 3, a downstream effector caspase, was higher in catagen hair then in other phases of the hair cycle, indicating a role in the terminal stage of the apoptotic pathway. Activated caspase 1 was also found in the hair bulb and hair shaft. .. Previously, the dermal papilla area of the hair follicle was thought to be the main control focus of cell regrowth and inhibition [25]. The findings from this study also suggest an important role of the upper-lower portion, infundibular area of the hair shaft where inner and outer root sheath are abruptly changing and that this area may play a role in the regulation of normal hair apoptosis. ….